ASS’N FOR MOLECULAR PATHOLOGY v. U.S. P.T.O. …...ASS’N FOR MOLECULAR PATHOLOGY v. U.S....

1303ASS’N FOR MOLECULAR PATHOLOGY v. U.S. P.T.O.Cite as 689 F.3d 1303 (Fed. Cir. 2012)

employee was receiving OWCP compensa-tion under FECA. 926 F.2d at 1156.

III. CONCLUSION

For the foregoing reasons, this courtreverses the decision of the Board withrespect to the statutory interpretation of‘‘resumes employment with the FederalGovernment,’’ and remands for determina-tion of the ‘‘rights and benefits based onlength of service’’ to which Gallo is entitledconsistent with this opinion.

REVERSED AND REMANDED

,

The ASSOCIATION FOR MOLECULARPATHOLOGY, The American Collegeof Medical Genetics, The AmericanSociety for Clinical Pathology, TheCollege of American Pathologists,Haig Kazazian, MD, Arupa Ganguly,PhD, Wendy Chung, MD, PhD, HarryOstrer, MD, David Ledbetter, PhD,Stephen Warren, PhD, Ellen Matloff,M.S., Elsa Reich, M.S., Breast CancerAction, Boston Women’s Health BookCollective, Lisbeth Ceriani, Runi Li-mary, Genae Girard, Patrice Fortune,Vicky Thomason, and Kathleen Rak-er, Plaintiffs–Appellees,

v.

UNITED STATES PATENT ANDTRADEMARK OFFICE,

Defendant,

and

Myriad Genetics, Inc., Defendant–Appellant,

and

Lorris Betz, Roger Boyer, Jack Brittain,Arnold B. Combe, Raymond Geste-land, James U. Jensen, John KendallMorris, Thomas Parks, David W.

Pershing, and Michael K. Young, intheir Official Capacity as Directors ofthe University of Utah ResearchFoundation, Defendants–Appellants.

No. 2010–1406.

United States Court of Appeals,Federal Circuit.

Aug. 16, 2012.

Background: Medical organizations, re-searchers, genetic counselors, and patientsbrought action against patentee and Pat-ent and Trademark Office (PTO), challeng-ing validity of patents for isolated deoxyri-bonucleic acid (DNA) sequences associatedwith predisposition to breast and ovariancancers and for diagnostic methods ofidentifying mutations in those DNA se-quences. Plaintiffs and patentee cross-moved for summary judgment, and PTOmoved for judgment on the pleadings. TheUnited States District Court for the South-ern District of New York, Robert W.Sweet, Senior District Judge, 702F.Supp.2d 181, granted PTO’s motion,granted plaintiffs’ motion in part, and de-nied patentee’s motion. Patentee appealed.The Court of Appeals, 653 F.3d 1329, af-firmed in part and reversed in part. Par-ties petitioned for certiorari, and the Unit-ed States Supreme Court, ––– U.S. ––––,132 S.Ct. 1794, 182 L.Ed.2d 613, grantedpetition and vacated and remanded.

Holdings: The Court of Appeals, Lourie,Circuit Judge, held that:

(1) only competitor with unequivocal in-tent to resume clinical diagnostic test-ing of DNA sequences had standing;

(2) various organizational plaintiffs lackedstanding;

(3) composition claims covering isolatedDNA sequences associated with predis-position to breast and ovarian cancerswere directed to patent-eligible subjectmatter;

1304 689 FEDERAL REPORTER, 3d SERIES

(4) claimed complementary deoxyribonu-cleic acids (cDNAs), which lacked non-coding introns in naturally occurringchromosomal DNA, were eligible forpatent;

(5) method claims for comparing or ana-lyzing isolated DNA sequences associ-ated with predisposition to breast andovarian cancers were not patentable;and

(6) method claim for screening potentialcancer therapeutics via changes in cellgrowth rates claimed patentable sub-ject matter.

Affirmed in part, reversed in part, andremanded.

Moore, Circuit Judge, filed opinion concur-ring in part.

Bryson, Circuit Judge, filed opinion con-curring in part and dissenting in part.

1. Federal Civil Procedure O103.2, 103.3The irreducible constitutional mini-

mum of standing requires a plaintiff tohave suffered an injury in fact, which is aninvasion of a legally protected interestwhich is concrete and particularized, andactual or imminent, not conjectural orhypothetical, there must be a causal con-nection between the injury and the con-duct complained of, i.e., the injury has tobe fairly traceable to the challenged actionof the defendant, and it must be likely, asopposed to merely speculative, that theinjury will be redressed by a favorabledecision. U.S.C.A. Const. Art. 3, § 1 etseq.

2. Courts O96(7)Whether an actual case or controversy

exists so that a district court may enter-tain an action for a declaratory judgmentof patent non-infringement or invalidity isgoverned by Federal Circuit law. 28U.S.C.A. § 2201(a).

3. Declaratory Judgment O393

In a patent case, the exercise of de-claratory judgment jurisdiction in light ofa particular set of facts is reviewed denovo.


Only competitor with unequivocal in-tent to resume clinical diagnostic testing ofdeoxyribonucleic acid (DNA) sequenceshad standing to bring action for declarato-ry judgment that patents for DNA se-quences and methods of testing sequencesfor cancer were invalid; competitor’s injurywas traceable to patentee’s enforcementactions that forced him to stop DNA test-ing, and favorable judgment on challengedclaims would remove absolute barrier tocompetitor’s ability to resume testing, butinjury to other competitors who allegedonly they would consider resuming testingwas insufficiently immediate to supporttheir standing. 28 U.S.C.A. § 2201(a).


Inability to afford a patented inven-tion could not establish invasion of a legal-ly protected interest for purposes of stand-ing in action seeking declaratory judgmentthat patent was invalid. U.S.C.A. Const.Art. 3, § 1 et seq.

6. Patents O289(2.1)

Laches bars the recovery of pre-filingdamages; it does not preclude a patentaction for prospective relief.


Just as active enforcement of patentrights against others can maintain a realand immediate controversy despite thepassage of time, so too can the successfulassertion of such rights when the relevantcircumstances remain unchanged.U.S.C.A. Const. Art. 3, § 1 et seq.


8. Declaratory Judgment O231.1A competitor need not risk liability

and treble damages for patent infringe-ment before seeking a declaration of hiscontested legal rights. 28 U.S.C.A.§ 2201(a).

9. Declaratory Judgment O232Competitors’ challenge to only portion

of composition and method claims of pat-ents for isolated deoxyribonucleic acid(DNA) sequences associated with predis-position to breast and ovarian cancers andfor diagnostic methods of identifying muta-tions in those DNA sequences was notspeculative, despite admitting that otherunchallenged claims would still preventthem from engaging in sequencing, sincecourt declined to construe asserted claimsand declined to hold on current record thatproposed activities would infringe unchal-lenged claims and alleged injury could beredressed by favorable decision. 28U.S.C.A. § 2201(a).

10. Declaratory Judgment O231.1Simply disagreeing with the existence

of a patent on isolated deoxyribonucleicacid (DNA) sequences or even suffering anattenuated, non-proximate, effect from theexistence of a patent does not meet therequirement for an adverse legal contro-versy of sufficient immediacy and realityto warrant the issuance of a declaratoryjudgment. 28 U.S.C.A. § 2201(a).

11. Associations O20(1) Declaratory Judgment O300

Various organizational plaintiffs thatwere not target of any enforcement actionor offered license agreements by patenteeand had not made preparation to under-take potentially infringing activities did notsuffer any injury and thus lacked standingto bring declaratory judgment actionagainst patentee and Patent and Trade-mark Office (PTO) to challenge validity ofpatents for isolated deoxyribonucleic acid(DNA) sequences associated with predis-

position to breast and ovarian cancers andfor diagnostic methods of identifying muta-tions in those DNA sequences. 28U.S.C.A. § 2201(a).

12. Patents O14

Composition claims covering isolateddeoxyribonucleic acid (DNA) sequences as-sociated with predisposition to breast andovarian cancers were directed to patent-eligible subject matter; isolated DNA wasnot only removed from its native cellularand chromosomal environment, but wasalso chemically manipulated to produce amolecule that was markedly different fromthat existing in the body. (Per Lourie,Circuit Judge, with one Circuit Judge con-curring in part and concurring in the judg-ment.) 35 U.S.C.A. § 101.

13. Patents O5, 6Laws of nature, natural phenomena,

and abstract ideas are not patentable. 35U.S.C.A. § 101.

14. Patents O191The basic right provided by a patent

is to exclude others from practicing thepatented subject matter.

15. Patents O14Claimed complementary deoxyribonu-

cleic acids (cDNAs), which lacked non-cod-ing introns in naturally occurring chromo-somal DNA, were eligible for patent ascompositions of matter distinct from natu-ral DNA, since they were result of humanintervention into nature. 35 U.S.C.A.§ 101.

16. Patents O14The distinctive nature of deoxyribonu-

cleic acid (DNA) molecules as isolatedcompositions of matter determines theirpatent eligibility rather than their physio-logical use or benefit; uses of chemicalsubstances may be relevant to the nonobvi-ousness of these substances or to method


claims embodying those uses, but the pat-ent eligibility of an isolated DNA is notnegated because it has similar information-al properties to a different, more complexnatural material. (Per Lourie, CircuitJudge, with Moore, Circuit Judge, concur-ring in the judgment.) 35 U.S.C.A. § 101.

17. Patents O179Genes are materials having a chemical

nature and, as such, are best described inpatents by their structures rather than bytheir functions, although biologists maythink of molecules in terms of their uses.

18. Patents O14Isolating genes to provide useful diag-

nostic tools and medicines is surely whatthe patent laws are intended to encourageand protect.

19. Patents O7.14Method claims for comparing or ana-

lyzing isolated DNA sequences associatedwith predisposition to breast and ovariancancers were directed to abstract mentalprocess, and thus were not patentable;claims did not include step of determiningDNA sequence by isolating genes fromblood sample and sequencing them, or anyother necessarily transformative step, but,rather, comparison between sequencescould be accomplished by mere inspectionalone. 35 U.S.C.A. § 101.

20. Patents O7.12The application of a formula or ab-

stract idea in a process may describe pat-ent-eligible subject matter. 35 U.S.C.A.§ 101.

21. Patents O7.14Method claim for screening potential

cancer therapeutics via changes in cellgrowth rates claimed patentable subjectmatter; although claim included steps ofdetermining cells’ growth rates and com-paring growth rates, claim applied certainsteps to man-made, non-naturally occur-ring transformed cells that were product

of man, not of nature, and it was tied tospecific host cells transformed with specificgenes and grown in presence or absence ofspecific type of therapeutic. 35 U.S.C.A.§ 101.

Patents O328(2)5,693,473, 5,747,282, 5,837,492. Valid.

Patents O328(2)5,709,999, 5,710,001, 5,753,441, 6,033,-

857. Invalid in Part.

Christopher A. Hansen, American CivilLiberties Union Foundation, of New York,NY, argued for plaintiffs-appellees. Withhim on the brief were Sandra S. Park,Aden Fine, and Lenora M. Lapidus. Ofcounsel on the brief were Daniel B. Ra-vicher and Sabrina Y. Hassan, Public Pat-ent Foundation, Benjamin N. Cardozo,School of Law, of New York, NY.

Gregory A. Castanias, Jones Day, ofWashington, DC, argued for all defendant-appellants. With him on the brief wereJennifer L. Swize, of Washington, DC, Is-rael Sasha Mayergoyz and Dennis Mu-rashko, of Chicago, IL, Brian M. Poissant,Laura A. Coruzzi and Eileen Falvey, ofNew York, NY. Of counsel were Benja-min Jackson, and Jay Z. Zhang, MyriadGenetics, of Salt Lake City, UT.

Melissa N. Patterson, Attorney, Civil Di-vision, Appellate Staff, United States De-partment of Justice, of Washington, DC,argued for amicus curiae, United States.With her on the brief were Stuart F. De-lery, Acting Assistant Attorney General,Beth S. Brinkmann, Deputy Assistant At-torney General and Scott R. McItosh, At-torney. Of counsel was Mark R. Freeman.

Thomas J. Kowalski, Vedder Price PC,of New York, New York, for amicus curiaeProtein Sciences Corporation. With him


on the brief were Deborah L. Lu; andRobert S. Rigg, of Chicago, IL.

Robert A. Armitage, Eli Lilly and Com-pany, Indianapolis, IN, for amicus curiae,Eli Lilly and Company. With him on thebrief was James J. Kelley.

Christopher M. Holman, University ofMissouri–Kansas City School of Law, ofKansas City, MO, for amicus curiae LawProfessor Christopher M. Holman.

Charles R. Macedo, Amster Rothstein &Ebenstein, LLP, of New York, NY, foramicus curiae, New York IntellectualProperty Law Association. Of counsel onthe brief were Ronald M. Daignault andMatthew B. McFarlane, Robins, Kaplan,Miller & Ciresi, L.L.P. of New York, NY.

Lori B. Andrews, IIT Chicago–KentCollege of Law, of Chicago, IL, for amicuscuriae, The American College of Embryol-ogy, et al. Of counsel was Joshua D.Sarnoff, DePaul University College ofLaw, of Chicago, IL.

Debra L. Greenfield, UCLA Institutefor Society and Genetics, of Los Angeles,CA, for amici curiae, The National Wom-en’s Health Network, et al.

Krista L. Cox, Knowledge Ecology In-ternational, of Washington, DC, for amicuscuriae, Knowledge Ecology International,et al.

Richard F. Phillips, Intellectual Proper-ty Owners Association, of Washington, DC,for amicus curiae, Intellectual PropertyOwners Association. With him on thebrief was Kevin H. Rhodes. Of counsel onthe brief were Paul H. Berghoff, Kevin E.Noonan and Jeffrey P. Armstrong,McDonnell Boehnen Hulbert & Berghoff,LLP, of Chicago, IL. Of counsel wereHerbert C. Wamsley, Intellectual PropertyOwners, of Washington, DC, and DouglasKent Norman, Eli Lilly & Company, ofIndianapolis, IN.

Barbara R. Rudolph, Finnegan,Henderson, Farabow, Garrett & Dunner,

LLP, of Washington, DC, for amicus curi-ae, American Intellectual Property LawAssociation. With her on the brief wereRobert D. Litowitz, Erika Harmon Arnerand David S. Forman. Of counsel on thebrief was William G. Barber, AmericanIntellectual Property Law Association, ofArlington, VA. Of counsel were DavidWarren Hill, American Intellectual Prop-erty, of Arlington, VA, and Robert C.Stanley, Finnegan, Henderson, Farabow,Garrett & Dunner, LLP, of Atlanta, GA.

William T. Robinson, III, American BarAssociation, of Chicago, IL, for amicus cu-riae, American Bar Association. Of coun-sel on the brief were John P. Elwood,Vinson & Elkins, LLP, of Washington,DC; and Michael A. Valek, Stephen C.Stout, of Austin, TX.

Mark J. Gatschet, Mark John Gatschet,P.L.L.C., of Houston, TX, for amicus curi-ae, Mark J. Gatschet and Richard W.Knight. Of counsel on the brief was Rich-ard W. Knight, R.W. Knight P.C. of SanAntonio, TX.

Claire Laporte, Foley Hoag, LLP, ofBoston, MA, for amicus curiae FederalCircuit Bar Association. With her on thebrief was James M. Flaherty, Jr.

John L. Hendricks, Hitchcock Evert,LLP, of Dallas, TX, for amicus curiae,AARP, et al. With him on the brief wereMegan M. O’Laughlin and John T. Tower.Of counsel was Michael R. Schuster.

J. Timothy Keane, Harness, Dickey &Pierce, PLC, of St. Louis, MO, for amicuscuriae, BioGenerator, et al.

Susan E. McBee, Baker, Donelson,Bearman, Caldwell, and Berkowitz, P.C.,of Washington, DC, for amicus curiae, Im-matics Biotechnologie, GmbH. With heron the brief was Bryan W. Jones.

Seth P. Waxman, Wilmer Cutler Picker-ing Hale and Dorr, LLP, of Washington,DC, for amicus curiae, Biotechnology In-


dustry Organization, et al. With him onthe brief was Thomas G. Saunders. Ofcounsel on the brief was Mark C. Fleming,of Boston, MA, and Hansjorg Salter, Bio-technology Industry Organization, ofWashington, DC. Of counsel was Allen C.Nunnally, Wilmer Cutler Pickering Haleand Dorr, LLP, of Boston, MA.

Jennifer Gordon, Baker Botts, L.L.P. ofNew York, NY, for amicus curiae, CroplifeInternational. With her on the brief wereSteven Lendaris and Jennifer C. Tempes-ta.

Matthew J. Dowd, Wiley Rein LLP, ofWashington, DC, for amicus curiae, JamesD. Watson. With him on the brief wasJames H. Wallace, Jr.

Kurt G. Calia, Covington & Burling,LLP, of Redwood Shores, CA, for amicuscuriae, Pharmaceutical Research and Man-ufacturers of America. With him on thebrief were Robert A. Long, Jr. and AllisonE. Kerndt, of Washington, DC, and AlexaR. Hansen, of San Francisco, CA.

Eileen M. Kane, Penn State DickinsonSchool of Law, of University Park, PA, foramicus curiae, Professor Eileen M. Kane.

Genevieve E. Scott, Yale School of Law,of Brooklyn, NY, for amicus curiae, Infor-mation Society Project at Yale Law SchoolScholars. With her on the brief was Pris-cilla J. Smith.

Robert Sachs, Fenwick & West, LLP, ofSan Francisco, CA, for amicus curiae, Ad-vanced Biological Laboratories, SA.

Before LOURIE, BRYSON, andMOORE, Circuit Judges.

Opinion for the court filed by CircuitJudge LOURIE. Opinion concurring inpart filed by Circuit Judge MOORE.Opinion concurring in part and dissentingin part filed by Circuit Judge BRYSON.

LOURIE, Circuit Judge.

Myriad Genetics, Inc. and the Directorsof the University of Utah Research Foun-dation (collectively, ‘‘Myriad’’) appeal fromthe decision of the United States DistrictCourt for the Southern District of NewYork holding that an assortment of medi-cal organizations, researchers, geneticcounselors, and patients (collectively,‘‘Plaintiffs’’) have standing under the De-claratory Judgment Act to challenge Myri-ad’s patents. Ass’n for Molecular Pathol-ogy v. U.S. Patent & Trademark Office,669 F.Supp.2d 365 (S.D.N.Y.2009) (‘‘DJOp.’’). Myriad also appeals from the dis-trict court’s decision granting summaryjudgment that all of the challenged claimsare drawn to non-patentable subject mat-ter under 35 U.S.C. § 101. Ass’n for Mo-lecular Pathology v. U.S. Patent & Trade-mark Office, 702 F.Supp.2d 181 (S.D.N.Y.2010) (‘‘SJ Op.’’). We affirm in part andreverse in part.

This appeal has returned to us as, apetition for certiorari having been filedfrom our decision of July 29, 2011, theSupreme Court of the United States grant-ed the petition, vacated our decision, andremanded the case to us for further con-sideration in light of its decision in MayoCollaborative Services v. Prometheus, Inc.,566 U.S. ––––, 132 S.Ct. 1289, 182 L.Ed.2d321 (2012). Ass’n for Molecular Pathologyv. Myriad Genetics, Inc., ––– U.S. ––––,132 S.Ct. 1794, 182 L.Ed.2d 613 (2012).We invited and received briefing by theparties and interested amici and held oralargument on July 20, 2012. Our decisionon remand follows. It both decides theissues that were before us in the originalappeal and evaluates the effect of Mayo onthose issues.

On the threshold issue of jurisdiction, weaffirm the district court’s decision to exer-cise declaratory judgment jurisdiction be-cause we conclude that at least one plain-


tiff, Dr. Harry Ostrer, has standing tochallenge the validity of Myriad’s patents.On the merits, we reverse the districtcourt’s decision that Myriad’s compositionclaims to ‘‘isolated’’ DNA molecules coverpatent-ineligible products of nature under§ 101 because each of the claimed mole-cules represents a nonnaturally occurringcomposition of matter. We also reversethe district court’s decision that Myriad’smethod claim to screening potential cancertherapeutics via changes in cell growthrates of transformed cells is directed to apatent-ineligible scientific principle. Weaffirm the court’s decision, however, thatMyriad’s method claims directed to ‘‘com-paring’’ or ‘‘analyzing’’ DNA sequences arepatent ineligible; such claims include notransformative steps and cover only pat-ent-ineligible abstract, mental steps.

BACKGROUND

Plaintiffs brought suit against Myriad,challenging the patentability of certaincomposition and method claims relating tohuman genetics. See DJ Op., 669F.Supp.2d at 369–76. Specifically, Plain-tiffs sought a declaration that fifteenclaims from seven patents assigned toMyriad are drawn to patent-ineligible sub-ject matter under 35 U.S.C. § 101: claims1, 2, 5, 6, 7, and 20 of U.S. Patent 5,747,282(‘‘the 8282 patent’’); claims 1, 6, and 7 ofU.S. Patent 5,837,492 (‘‘the 8492 patent’’);claim 1 of U.S. Patent 5,693,473 (‘‘the 8473patent’’); claim 1 of U.S. Patent 5,709,999(‘‘the 8999 patent’’); claim 1 of U.S. Patent5,710,001 (‘‘the 8001 patent’’); claim 1 ofU.S. Patent 5,753,441 (‘‘the 8441 patent’’);and claims 1 and 2 of U.S. Patent 6,033,857(‘‘the 8857 patent’’).

The challenged composition claims covertwo ‘‘isolated’’ human genes, BRCA1 andBRCA2 (collectively, ‘‘BRCA1/2 ’’ or

‘‘BRCA ’’), and certain alterations, or mu-tations, in these genes associated with apredisposition to breast and ovarian can-cers. Representative composition claimsinclude claims 1, 2, and 5 of the 8282patent:

1. An isolated DNA coding for aBRCA1 polypeptide, said polypeptidehaving the amino acid sequence set forthin SEQ ID NO:2.2. The isolated DNA of claim 1, where-in said DNA has the nucleotide sequenceset forth in SEQ ID NO:1.5. An isolated DNA having at least 15nucleotides of the DNA of claim 1.

8282 patent col. 153 1.55—col. 154 1.56.1

SEQ ID NO:2 depicts the amino acid se-quence of the BRCA1 protein, and SEQID NO:1 depicts the nucleotide sequenceof the BRCA1 DNA coding region; thelatter sequence is colloquially referred toas cDNA. Id. col. 19 ll.48–50.

All but one of the challenged methodclaims cover methods of ‘‘analyzing’’ or‘‘comparing’’ a patient’s BRCA sequencewith the normal, or wild-type, sequence toidentify the presence of cancer-predispos-ing mutations. Representative methodclaims include claims 1 of the 8999 and 8001patents:

1. A method for detecting a germlinealteration in a BRCA1 gene, said altera-tion selected from the group consistingof the alterations set forth in Tables12A, 14, 18 or 19 in a human whichcomprises analyzing a sequence of aBRCA1 gene or BRCA1 RNA from ahuman sample or analyzing a sequenceof BRCA1 cDNA made from mRNAfrom said human sample with the provi-so that said germline alteration is not adeletion of 4 nucleotides correspondingto base numbers 4184–4187 of SEQ IDNO: 1.

1. In addition to representative claims 1, 2,and 5 of the 8282 patent, other claims toisolated DNA molecules at issue in this appeal

include: claims 6 and 7 of the 8282 patent;claims 1, 6, and 7 of the 8492 patent; andclaim 1 of the 8473 patent.


8999 patent col. 161 ll.17–25 (emphasesadded).

1. A method for screening a tumorsample from a human subject for a so-matic alteration in a BRCA1 gene insaid tumor which comprises [ ] compar-ing a first sequence selected from thegroup consisting of a BRCA1 gene fromsaid tumor sample, BRCA1 RNA fromsaid tumor sample and BRCA1 cDNAmade from mRNA from said tumor sam-ple with a second sequence selectedfrom the group consisting of BRCA1gene from a nontumor sample of saidsubject, BRCA1 RNA from said nontu-mor sample and BRCA1 cDNA madefrom mRNA from said nontumor sam-ple, wherein a difference in the sequenceof the BRCA1 gene, BRCA1 RNA orBRCA1 cDNA from said tumor samplefrom the sequence of the BRCA1 gene,BRCA1 RNA or BRCA1 cDNA fromsaid nontumor sample indicates a somat-ic alteration in the BRCA1 gene in saidtumor sample.

8001 patent col.155 ll.2–17 (emphasis add-ed).2

The final method claim challenged byPlaintiffs is directed to a method of screen-ing potential cancer therapeutics. Specifi-cally, claim 20 of the 8282 patent reads asfollows:

20. A method for screening potentialcancer therapeutics which comprises:growing a transformed eukaryotic hostcell containing an altered BRCA1 genecausing cancer in the presence of a com-pound suspected of being a cancer ther-apeutic, growing said transformed euka-

ryotic host cell in the absence of saidcompound, determining the rate ofgrowth of said host cell in the presenceof said compound and the rate of growthof said host cell in the absence of saidcompound and comparing the growthrate of said host cells, wherein a slowerrate of growth of said host cell in thepresence of said compound is indicativeof a cancer therapeutic.

8282 patent col. 156 ll.13–24 (emphasesadded).

The challenged claims thus relate to iso-lated gene sequences and diagnostic meth-ods of identifying mutations in these se-quences. To place this suit in context, wetake a step back to provide background onthe science involved, including the identifi-cation of the BRCA genes, and the Plain-tiffs’ connections to the invention and toMyriad.

I.

Human genetics is the study of heredityin human beings.3 The human genome,the entirety of human genetic information,contains approximately 22,000 genes,which form the basis of human inheritance.The majority of genes act by guiding theproduction of polypeptide chains that formproteins. Proteins in turn make up havingmatter and catalyze a variety of cellularprocesses.

Chemically, the human genome is com-posed of deoxyribonucleic acid (‘‘DNA’’).Each DNA molecule is made up of repeat-ing units of four nucleotide bases—adenine(‘‘A’’), thymine (‘‘T’’), cytosine (‘‘C’’), andguanine (‘‘G’’)—which are covalentlylinked, or bonded,4 together via a sugar-

2. The claims currently before us that recitemethods of ‘‘analyzing’’ or ‘‘comparing’’BRCA sequences are: claims 1 of the 8999,8001, and 8441 patents and claims 1 and 2 ofthe 8857 patent.

3. The district court’s opinion, SJ Op., 702F.Supp.2d at 192–203, contains a detailed

and comprehensive discussion of the scienceinvolved in this case. We repeat only thebasics here.

4. Covalent bonds are chemical bonds charac-terized by the sharing of electrons betweenatoms in a molecule.


phosphate, or phosphodiester, backbone.DNA generally exists as two DNA strandsintertwined as a double helix in which eachbase on a strand pairs, or hybridizes, witha complementary base on the other strand:

A pairs with T, and C with G. Figure 1below depicts the structure of a DNA dou-ble helix and the complementary pairing ofthe four nucleotide bases, represented byA, T, C, and G.

The linear order of nucleotide bases in aDNA molecule is referred to as its ‘‘se-quence.’’ The sequence of a gene is thusdenoted by a linear sequence of As, Ts, Gs,and Cs. ‘‘DNA sequencing’’ or ‘‘gene se-quencing’’ refers to the process by whichthe precise linear order of nucleotides in aDNA segment or gene is determined. Agene’s nucleotide sequence in turn encodesfor a linear sequence of amino acids thatcomprise the protein encoded by the gene,e.g., the BRCA1 gene encodes for theBRCA1 protein. Most genes have both‘‘exon’’ and ‘‘intron’’ sequences. Exons areDNA segments that are necessary for thecreation of a protein, i.e., that code for aprotein. Introns are segments of DNAinterspersed between the exons that, un-like exons, do not code for a protein.

The creation of a protein from a genecomprises two steps: transcription andtranslation. First, the gene sequence is‘‘transcribed’’ into a different nucleic acidcalled ribonucleic acid (‘‘RNA’’). RNA has

a chemically different sugar-phosphatebackbone than DNA, and it utilizes thenucleotide base uracil (‘‘U’’) in place ofthymine (‘‘T’’). During transcription, theDNA double helix is unwound and eachnucleotide on the non-coding, or template,DNA strand is used to make a complemen-tary, single-stranded RNA molecule thatmirrors the coding DNA strand, i.e., ade-nine on the template DNA strand resultsin uracil in the RNA molecule, thymineresults in adenine, guanine in cytosine, andcytosine in guanine. The resulting ‘‘pre-RNA,’’ like the DNA from which it wasgenerated, contains both exon and intronsequences. Next, the introns are physical-ly excised from the pre-RNA molecule,followed by ‘‘splicing’’ the exons to producea messenger RNA (‘‘mRNA’’). Figure 2below shows the steps of transcribing agene that contains three exons (exon 1–3)and two introns (intron 1 and 2) into a pre-RNA, followed by RNA excising the in-trons and splicing of the exons to producean mRNA containing only exon sequences.


Following transcription and splicing, theresulting mRNA is ‘‘translated’’ into theencoded protein. Genes, and their corre-sponding mRNAs, encode proteins viathree-nucleotide combinations called co-dons. Each codon triplet corresponds toone of the twenty amino acids that makeup all proteins or a ‘‘stop’’ signal thatterminates protein translation. For exam-ple, the codon adenine-thymine-guanine(ATG, or AUG in the correspondingmRNA), encodes the amino acid methio-nine. The relationship between the sixty-four possible codon sequences and theircorresponding amino acids is known as thegenetic code. Figure 3 below representsan mRNA molecule that translates into aprotein of six amino acids (Codon 1, AUG,methionine; Codon 2, ACG, threonine;Codon 3, GAG, glutamic acid; Codon 4,CUU, leucine; Codon 5, CGG, arginine;Codon 6, AGC, serine), and ends with oneof the three stop codons, UAG.

Changes, or mutations, in the sequenceof a human gene can alter the production,structure, and/or function of the resultingprotein. Small-scale changes include pointmutations in which a change to a singlenucleotide alters a single amino acid in theencoded protein. For example, a basechange in the codon GCU to CCU changesan alanine in the encoded protein to aproline. Larger scale variations includethe deletion, rearrangement, or duplicationof larger DNA segments—ranging fromseveral hundreds to over a million nucleo-


tides—and can result in the elimination,misplacement, or duplication of an entiregene or genes. While some mutationshave little or no effect on the body’s pro-cesses, others result in disease or an in-creased risk of developing a particular dis-ease. DNA sequencing is used in clinicaldiagnostic testing to determine whether agene contains mutations associated with aparticular disease or disease risk.

Nearly every cell in the human bodycontains an individual’s entire genome.DNA in the cell, called ‘‘native’’ or ‘‘ge-nomic’’ DNA, is packaged into twenty-three pairs of chromosomes. Chromo-somes are complex structures comprising asingle extended DNA molecule wrappedaround proteins called histones, as shownin Figure 4 below.

Each chromosome contiguously spans mil-lions of bases and encompasses many dis-crete genes. Humans have twenty-twopairs of autosomal chromosomes, num-bered one to twenty-two according to sizefrom largest to smallest, and one pair ofsex chromosomes, two X chromosomes infemales and one X and one Y chromosomein males.

Genomic DNA can be extracted from itscellular environment using a number ofwell-established laboratory techniques. Aparticular segment of DNA, such as a

gene, can then be excised or amplifiedfrom the DNA to obtain the isolated DNAsegment of interest. DNA molecules canalso be synthesized in the laboratory. Onetype of synthetic DNA molecule is comple-mentary DNA (‘‘cDNA’’). cDNA is synthe-sized from mRNA using complementarybase pairing in a manner analogous toRNA transcription. The process results ina double-stranded DNA molecule with asequence corresponding to the sequence ofan mRNA produced by the body. Becauseit is synthesized from mRNA, cDNA con-tains only the exon sequences, and thus


none of the intron sequences, from a chro-mosomal gene sequence.

II.

Certain mutations in the BRCA genescorrelate with an increased risk of breastand ovarian cancer. The average womanin the United States has around a twelveto thirteen percent risk of developingbreast cancer in her lifetime. Women withBRCA mutations, in contrast, face a cumu-lative risk of between fifty to eighty per-cent of developing breast cancer and acumulative risk of ovarian cancer of be-tween twenty to fifty percent. Diagnosticgenetic testing for the existence of BRCAmutations is therefore an important con-sideration in the provision of clinical carefor breast or ovarian cancer. This testingprovides a patient with information on herrisk for hereditary breast and ovarian can-cers, and thus aids in the difficult decisionregarding whether to undertake preven-tive options, including prophylactic sur-gery. Diagnostic results can also be animportant factor in structuring an appro-priate course of cancer treatment, sincecertain forms of therapy are more effectivein treating cancers related to BRCA muta-tions.

The inventors of the patents in suit iden-tified the genetic basis of BRCA1– andBRCA2-related cancers using an analysiscalled positional cloning. Relying on alarge set of DNA samples from familieswith inherited breast and ovarian cancers,the inventors correlated the occurrence ofcancer in individual family members withthe inheritance of certain marker DNAsequences. This allowed the inventors toidentify, or ‘‘map,’’ the physical location of

the BRCA genes within the human ge-nome and to isolate the BRCA genes anddetermine their exact nucleotide se-quences. This in turn allowed Myriad toprovide BRCA diagnostic testing servicesto women.5

III.

Myriad, however, was not the only enti-ty to implement clinical BRCA testing ser-vices. Starting in 1996, the University ofPennsylvania’s Genetic Diagnostic Labora-tory (‘‘GDL’’), co-directed by plaintiffsHaig H. Kazazian, Jr., M.D. and ArupaGanguly, Ph.D., provided BRCA1/2 diag-nostic services to women. By 1999, how-ever, accusations by Myriad that GDL’sBRCA testing services infringed its pat-ents forced the lab to stop providing suchservices.

The first sign of a dispute came in ear-ly 1998. At that time, Dr. Kazazian re-calls a dinner with Dr. Mark Skolnick,inventor and Chief Science Officer atMyriad. At the dinner, Skolnick informedKazazian that Myriad was planning tostop GDL from providing clinical BRCAtesting in light of Myriad’s patents. Amonth or two later, in May 1998, Kazazi-an received a letter from William A.Hockett, Director of Corporate Communi-cations at Myriad. The letter stated thatMyriad knew that Kazazian was currentlyproviding BRCA1 diagnostic testing ser-vices, and that Myriad, as patent holderof five U.S. patents covering the isolatedBRCA1 gene and diagnostic testing, wasmaking available to select institutions acollaborative license. Attached to the let-ter was a copy of Myriad’s collaborative

5. Myriad filed the first patent applicationleading to the patents in suit covering isolatedBRCA1 DNA and associated diagnostic meth-ods in August 1994. The first resulting pat-ent, the 8473 patent, issued on December 2,1997. Myriad filed the first application lead-

ing to the patents in suit covering isolatedBRCA2 DNA and associated diagnostic meth-ods in December 1995, and the first suchpatent, the 8492 patent, issued on November17, 1998.


agreement, which proposed severely limit-ing GDL’s testing services to certain testsfor patients of Ashkenazi Jewish descent.Plaintiff Harry Ostrer, M.D., a researcherat New York University (‘‘NYU’’) Schoolof Medicine, received the same letter andcollaborative agreement in May 1998, al-though his laboratory did not, at the time,provide such testing services. Rather,Ostrer sent patient samples to GDL forBRCA genetic testing.

Months later, in August 1998, Dr. Kaza-zian received a second letter, this timefrom George A. Riley of the law firmO’Melveny & Myers LLP. The letter iden-tified by number five Myriad patents ‘‘cov-ering, among other things, the BRCA1gene sequence TTT and methods for detect-ing alterations in the BRCA1 sequence.’’J.A. 1145. The letter also indicated that it‘‘has come to Myriad’s attention that youare engaged in commercial testing activi-ties that infringe Myriad’s patents,’’ andthat ‘‘[u]nless and until a licensing ar-rangement is completed TTT you shouldcease all infringing testing activity.’’ Id.The letter noted, however, that the cease-and-desist notification did not apply to re-search testing ‘‘for the purpose of further-ing non-commercial research programs,the results of which are not provided tothe patient and for which no money isreceived from the patient or the patient’sinsurance.’’ Id.

In June 1999, Robert Terrell, the Gener-al Counsel for the University of Pennsylva-nia, received a similar cease-and-desist let-ter from Christopher Wight, Myriad’sGeneral Counsel. The letter stated, ‘‘Ithas come to our attention that Dr. Haig H.Kazazian, Jr. of the University of Pennsyl-vania is continuing to willfully engage incommercial BRCA1 and BRCA2 genetictesting activities, in violation of the Uni-versity of Pennsylvania’s previous assur-ances that such commercial testing activi-ties would be discontinued.’’ J.A. 2890.

Terrell responded to Wight by letter onSeptember 10, 1999, stating that ‘‘the Uni-versity agrees that it will not accept sam-ples for BRCA1 research testing fromthird parties.’’ J.A. 2891. Kazazian thusinformed Dr. Ostrer that GDL would nolonger be accepting patient samples forBRCA testing from him or anyone else asa result of the patent infringement asser-tions made by Myriad. As a result, Ostrerstarted sending patient samples for BRCAgenetic testing to Myriad, which became(and remains today) the only provider ofsuch services in the United States.

During this period, Myriad also initiatedseveral patent infringement suits againstentities providing clinical BRCA testing.Myriad filed suit against Oncormed Inc. in1997 and again in 1998, Myriad Genetics v.Oncormed, Nos. 2:97–cv–922, 2:98–cv–35(D.Utah), and the University of Pennsylva-nia in 1998, Myriad Genetics v. Univ. ofPa., No. 2:98–cv–829 (D.Utah). Both law-suits were later dismissed without preju-dice after each defendant agreed to discon-tinue all allegedly infringing activity.

None of the plaintiffs besides Drs. Kaza-zian, Ganguly, and Ostrer, allege that Myr-iad directed any letters or other communi-cations regarding its patents at them.Rather, the other researchers and medicalorganization members state simply thatknowledge of Myriad’s vigorous enforce-ment of its patent rights against othersstopped them from engaging in clinicalBRCA genetic testing, although they havethe personnel, expertise, and facilities aswell as the desire to provide such testing.The patient plaintiffs state that they havebeen unable to obtain any BRCA genetictesting or their desired BRCA testing, ei-ther covered by their insurance or at aprice that they can afford, because of Myr-iad’s patent protection.

Like the other researchers, Dr. Kazazi-an states that if Myriad’s patents were


held invalid, he and Dr. Ganguly would beable to resume BRCA testing within amatter of a few weeks. He notes, howev-er, that this is only if they ‘‘decided toresume BRCA testing.’’ J.A. 2852. Gan-guly concurs, stating that if the patentswere invalidated, ‘‘I would immediatelyconsider resuming BRCA testing in mylaboratory.’’ J.A. 2892. Dr. Ostrer 6 alsoindicates that his lab has all the personnel,facilities, and expertise necessary to un-dertake clinical BRCA testing and em-phatically states that his lab ‘‘would imme-diately begin to perform BRCA1/2–relatedgenetic testing upon invalidation of theMyriad patents.’’ J.A. 2936–38.

IV.

After Plaintiffs filed suit, Myriad movedto have the case dismissed, alleging thatthe Plaintiffs lacked standing to bring adeclaratory judgment suit challenging thevalidity of its patents. The district courtdisagreed, however, holding that the Plain-tiffs had established Article III standingunder the ‘‘all the circumstances’’ test ar-ticulated by the Supreme Court in MedIm-mune, Inc. v. Genentech, Inc., 549 U.S.118, 127, 127 S.Ct. 764, 166 L.Ed.2d 604(2007). DJ Op., 669 F.Supp.2d at 385–92.The court first found that Myriad hadengaged in sufficient ‘‘affirmative acts’’based on the company’s assertion of its‘‘right to preclude others from engaging inBRCA1/2 genetic testing through personalcommunications, cease-and-desist letters,licensing offers, and litigation,’’ the resultof which was ‘‘the widespread understand-

ing that one may engage in BRCA1/2 test-ing at the risk of being sued for infringe-ment liability by Myriad.’’ Id. at 390.Myriad’s actions, the court concluded, hadplaced ‘‘the Plaintiffs in precisely the situa-tion that the Declaratory Judgment Actwas designed to address: the Plaintiffshave the ability and desire to engage inBRCA1/2 testing as well as the belief thatsuch testing is within their rights, butcannot do so without risking infringementliability.’’ Id.

In so holding, the court rejected Myri-ad’s argument that there must be some actdirected toward the Plaintiffs, noting thatMyriad had, in fact, taken affirmative actstoward plaintiffs Dr. Kazazian and Dr.Ganguly. Id. at 387–88. The court alsorejected Myriad’s arguments that thecease-and-desist letter sent to plaintiff Ka-zazian was too old to support declaratoryjudgment jurisdiction and that the legalactions brought against third parties couldnot be considered in the jurisdictionalanalysis. Id. at 388–89. The court con-cluded that rigid adherence to either ofthese requirements would be inconsistentwith MedImmune’s mandate that thecourt assess the facts alleged under all thecircumstances. Id.

The district court also found that thePlaintiffs had alleged sufficient meaningfulpreparations for infringement to establishdeclaratory judgment jurisdiction. Id. at390–92. With respect to the researchers,the court held it was sufficient that theywere all ‘‘ready, willing, and able’’ to begin

6. On July 27, 2011, two days before we issuedour initial, now-vacated decision in this case,Myriad notified the court that Dr. Ostrer wasleaving NYU to assume a position at the Al-bert Einstein College of Medicine and Montef-iore Medical Center, effective August 29,2011. In response, Plaintiffs submitted a sup-plemental declaration from Dr. Ostrer statingthat, in his new position, he still seeks toundertake BRCA diagnostic testing, still has

the resources and expertise to conduct suchtesting, and would immediately do so if Myri-ad’s patents were invalidated. Following re-mand from the Supreme Court, we have alsoreceived from Myriad a related ‘‘suggestion ofmootness’’ and motion to remand or dismiss.We declined the suggestion and denied themotion. We now review this case on the factsand arguments briefed and presented to us.


BRCA1/2 testing within the normal courseof their laboratories’ research, rejectingMyriad’s argument that they needed toallege specific preparatory activities. Id.at 390–91. The court also rejected Myri-ad’s argument that plaintiffs Kazazian andGanguly testified only that they would‘‘consider’’ engaging in allegedly infringingactivities, concluding that the proper focusof the inquiry is whether they are mean-ingfully prepared, not whether they havemade a final, conclusive decision to engagein such activities. Id. at 391 n. 18.

The parties then moved for summaryjudgment on the merits of Plaintiffs’ § 101challenge to Myriad’s patent claims. Thedistrict court held for Plaintiffs, concludingthat the fifteen challenged claims weredrawn to non-patentable subject matterand thus invalid under § 101. SJ Op., 702F.Supp.2d at 220–37. Regarding the com-position claims, the court held that isolatedDNA molecules fall within the judiciallycreated ‘‘products of nature’’ exception to§ 101 because such isolated DNAs are not‘‘markedly different’’ from native DNAs.Id. at 222, 232 (quoting Diamond v. Chak-rabarty, 447 U.S. 303, 100 S.Ct. 2204, 65L.Ed.2d 144 (1980)). The court relied onthe fact that, unlike other biological mole-cules, DNAs are the ‘‘physical embodimentof information,’’ and that this informationis not only preserved in the claimed isolat-ed DNA molecules, but also essential totheir utility as molecular tools. Id. at 228–32.

Turning to the method claims, the courtheld them patent ineligible under thiscourt’s then-definitive machine-or-transfor-mation test. Id. at 233 (citing In re Bil-ski, 545 F.3d 943 (Fed.Cir.2008) (en banc),aff’d on other grounds, Bilski v. Kappos,––– U.S. ––––, 130 S.Ct. 3218, 3225, 177L.Ed.2d 792 (2010)). The court held thatthe claims covered ‘‘analyzing’’ or ‘‘com-paring’’ DNA sequences by any method,and thus covered mental processes inde-

pendent of any physical transformations.Id. at 233–35. In so holding, the court dis-tinguished Myriad’s claims from those atissue in Mayo based on the ‘‘determining’’step in the latter being construed to in-clude the extraction and measurement ofmetabolite levels from a patient sample.SJ Op., 702 F.Supp.2d at 234–35 (citingPrometheus Labs., Inc. v. Mayo Collabo-rative Servs., 628 F.3d 1347, 1350 (Fed.Cir.2010), rev’d, ––– U.S. ––––, 132 S.Ct.1289, 182 L.Ed.2d 321 (2012)). Alterna-tively, the court continued, even if theclaims could be read to include the trans-formations associated with isolating andsequencing human DNA, these transfor-mations would constitute no more thanpreparatory data-gathering steps. Id. at236 (citing In re Grams, 888 F.2d 835, 840(Fed.Cir.1989)). Finally, the court heldthat the one method claim to ‘‘comparing’’the growth rate of cells claimed a basicscientific principle and that the transfor-mative steps amounted to only preparato-ry data gathering. Id. at 237.

Myriad appealed. We have jurisdictionpursuant to 28 U.S.C. § 1295(a)(1).

DISCUSSION

I. Declaratory Judgment Jurisdiction

A.

The first question we must address iswhether the district court correctly exer-cised declaratory judgment jurisdictionover this suit. The Declaratory JudgmentAct provides that, ‘‘In a case of actualcontroversy within its jurisdiction TTT anycourt of the United States TTT may declarethe rights and other legal relations of anyinterested party seeking such declaration,whether or not further relief is or could besought.’’ 28 U.S.C. § 2201(a). Thephrase ‘‘a case of actual controversy’’ inthe Act refers to the types of ‘‘cases’’ and‘‘controversies’’ that are justiciable under


Article III of the U.S. Constitution. Aet-na Life Ins. v. Haworth, 300 U.S. 227,239–40, 57 S.Ct. 461, 81 L.Ed. 617 (1937).

Although no bright-line rule exists fordetermining whether a declaratory judg-ment action satisfies Article Ill’s case-or-controversy requirement, the SupremeCourt has held that the dispute must be‘‘definite and concrete, touching the legalrelations of parties having adverse legalinterests,’’ ‘‘real and substantial,’’ and‘‘admi[t] of specific relief through a decreeof a conclusive character, as distinguishedfrom an opinion advising what the lawwould be upon a hypothetical state offacts.’’ MedImmune, 549 U.S. at 127, 127S.Ct. 764 (quoting Aetna Life, 300 U.S. at240–41, 57 S.Ct. 461). ‘‘Basically, thequestion in each case is whether the factsalleged, under all the circumstances, showthat there is a substantial controversy, be-tween parties having adverse legal inter-ests, of sufficient immediacy and reality towarrant the issuance of a declaratory judg-ment.’’ Id. (quoting Md. Cas. Co. v. Pac.Coal & Oil Co., 312 U.S. 270, 273, 61 S.Ct.510, 85 L.Ed. 826 (1941)).

In applying MedImmune’s all-the-cir-cumstances test to a declaratory judgmentaction, we are guided by the SupremeCourt’s three-part framework for deter-mining whether an action presents a justi-ciable Article III controversy: standing,ripeness, and mootness. See CaracoPharm. Labs., Ltd. v. Forest Labs., Inc.,527 F.3d 1278, 1291 (Fed.Cir.2008). Inthis case, the parties have framed the ju-risdictional issue as one of standing. SeeMedImmune, 549 U.S. at 128 n. 8, 127S.Ct. 764. (‘‘The justiciability problem thatarises, when the party seeking declaratoryrelief is himself preventing the com-plained-of injury from occurring, can bedescribed in terms of standing TTT or TTT

ripeness.’’ (internal citations omitted)).

[1] ‘‘[T]he irreducible constitutionalminimum of standing contains three ele-

ments.’’ Lujan v. Defenders of Wildlife,504 U.S. 555, 560, 112 S.Ct. 2130, 119L.Ed.2d 351 (1992). ‘‘First, the plaintiffmust have suffered an injury in fact—aninvasion of a legally protected interestwhich is (a) concrete and particularized,and (b) actual or imminent, not conjecturalor hypothetical.’’ Id. (internal citationsand quotations omitted). ‘‘Second, theremust be a causal connection between theinjury and the conduct complained of—theinjury has to be ‘fairly TTT trace [able] tothe challenged action of the defen-dantTTTT’ ’’ Id. (quoting Simon v. E. Ky.Welfare Rights Org., 426 U.S. 26, 41–42, 96S.Ct. 1917, 48 L.Ed.2d 450 (1976)).‘‘Third, it must be ‘likely,’ as opposed tomerely ‘speculative,’ that the injury will be‘redressed by a favorable decision.’ ’’ Id. at561, 112 S.Ct. 2130 (quoting Simon, 426U.S. at 38, 43, 96 S.Ct. 1917).

[2, 3] ‘‘Whether an actual case or con-troversy exists so that a district court mayentertain an action for a declaratory judg-ment of non-infringement and/or invalidityis governed by Federal Circuit law.’’MedImmune, Inc. v. Centocor, Inc., 409F.3d 1376, 1378 (Fed.Cir.2005), overruledon other grounds, MedImmune, 549 U.S.at 130–31, 127 S.Ct. 764. Following Med-Immune, this court has held that, to estab-lish an injury in fact traceable to the pat-entee, a declaratory judgment plaintiffmust allege both (1) an affirmative act bythe patentee related to the enforcement ofhis patent rights, SanDisk Corp. v. STMi-croelecs., Inc., 480 F.3d 1372, 1380–81(Fed.Cir.2007), and (2) meaningful prepa-ration to conduct potentially infringing ac-tivity, Cat Tech LLC v. TubeMaster, Inc.,528 F.3d 871, 880 (Fed.Cir.2008). We re-view the exercise of declaratory judgmentjurisdiction in light of a particular set offacts de novo. SanDisk Corp., 480 F.3d at1377.


B.

[4] Myriad challenges the districtcourt’s jurisdictional decision on thegrounds that Myriad and the Plaintiffs donot have adverse legal interests and thatPlaintiffs have failed to allege a controver-sy of sufficient immediacy and reality towarrant the issuance of a declaratory judg-ment. Specifically, Myriad argues thatPlaintiffs have failed to allege any ‘‘affir-mative acts’’ by Myriad within the past tenyears relating to the patents in suit ordirected at any Plaintiff. According toMyriad, the district court erred by relyingon ‘‘stale communications’’ directed at Drs.Kazazian, Ganguly, and Ostrer over a dec-ade ago, as well as ten-year-old licensingand litigation activities directed at thirdparties, and thus exercised jurisdictionbased solely on Plaintiffs’ subjective fearof suit, arising from rumor and innuendoin the research community.

Plaintiffs respond that they have stand-ing under MedImmune’s all-the-circum-stances test because, not only are theyundisputedly prepared to immediately un-dertake potentially infringing activities,but also Myriad took sufficient affirmativeacts with respect to the patents in suit.Regarding the latter, Plaintiffs assert thatMyriad sued, threatened to sue, or de-manded license agreements from everyknown institution offering BRCA clinicaltesting, including university labs directedby plaintiffs Kazazian, Ganguly, and Ostr-er, forcing each to cease such testing.And, according to Plaintiffs, the awarenessof Myriad’s vigorous assertion of its patentrights still continues to suppress their abil-ity to perform clinical BRCA testing, plac-ing Plaintiffs in the very dilemma the De-

claratory Judgment Act was intended toaddress: they must either proceed withBRCA-related activities and risk liabilityfor patent infringement, or refrain fromsuch activities despite believing Myriad’spatents are invalid.

[5] Under the facts alleged in thiscase, we conclude that one Plaintiff, Dr.Ostrer, has established standing to main-tain this declaratory judgment suit. AllPlaintiffs claim standing under the Declar-atory Judgment Act based on the samealleged injury: that they cannot undertakethe BRCA-related activities that they de-sire because of Myriad’s enforcement of itspatent rights covering BRCA1/2.7 Onlythree plaintiffs, however, allege an injurytraceable to Myriad; only Drs. Kazazian,Ganguly, and Ostrer allege affirmative pat-ent enforcement actions directed at themby Myriad. Of these three, Dr. Ostrerclearly alleges a sufficiently real and immi-nent injury because he alleges an intentionto actually and immediately engage in al-legedly infringing BRCA-related activities.We address each in turn.

Although MedImmune relaxed thiscourt’s more restrictive ‘‘reasonable appre-hension of suit’’ test for declaratory judg-ment jurisdiction, SanDisk, 480 F.3d at1380, it did not alter ‘‘the bedrock rule thata case or controversy must be based on areal and immediate injury or threat offuture injury that is caused by the defen-dants,’’ Prasco, LLC v. Medicis Pharm.Corp., 537 F.3d 1329, 1339 (Fed.Cir.2008).Accordingly, following MedImmune, thiscourt has continued to hold that declarato-ry judgment jurisdiction will not arisemerely on the basis that a party learns of

7. Certain patients also allege an injury basedon their inability to gain access to affordableBRCA genetic testing because of Myriad’s pat-ent dominance of such services. While denialof health services can, in certain circum-stances, state a judicially cognizable injury,see Simon, 426 U.S. at 40–41, 96 S.Ct. 1917,

Plaintiffs have not pressed this as an indepen-dent ground for standing. Moreover, we failto see how the inability to afford a patentedinvention could establish an invasion of alegally protected interest for purposes ofstanding.


the existence of an adversely held patent,or even perceives that such a patent posesa risk of infringement, in the absence ofsome affirmative act by the patentee.SanDisk, 480 F.3d at 1380–81. Thus,without defining the outer boundaries ofdeclaratory judgment jurisdiction, we haveheld that ‘‘where a patentee asserts rightsunder a patent based on certain identifiedongoing or planned activity of another par-ty, and where that party contends that ithas the right to engage in the accusedactivity without license, an Article III caseor controversy will ariseTTTT’’ Id. at 1381;see also Prasco, 537 F.3d at 1338 (‘‘Apatentee can cause TTT an injury [suffi-cient to create an actual controversy] in avariety of ways, for example, by creating areasonable apprehension of an infringe-ment suit, [or] demanding the right toroyalty payments.’’ (internal citations omit-ted)).

In this case, Myriad demanded a royaltyunder its patents from Dr. Ostrer based onhis clinical BRCA-related activities. InMay 1998, Myriad’s Director of CorporateCommunications sent Ostrer a letter pro-posing a collaborative license. The letterstated that Myriad was aware that Ostrerwas either currently providing, or was in-terested in initiating, BRCA1 diagnostictesting services and that Myriad, as holderof U.S. patents covering the BRCA1 geneand diagnostic testing of BRCA1, wasmaking available to his institution, NYUMedical Center, a limited collaborative li-cense. The collaborative license requiredNYU to make a payment to Myriad foreach non-research BRCA test performed.

At the same time, as Ostrer was aware,Myriad was asserting its patent rightsagainst other similarly situated parties, afact to be considered in assessing the exis-tence of an actual controversy under thetotality of circumstances. See MicronTech., Inc. v. Mosaid Techs., Inc., 518F.3d 897, 901 (Fed.Cir.2008). Soon after

Ostrer received Myriad’s letter, Dr. Kaza-zian informed him that, because of Myri-ad’s assertion of its patent rights againsthim, GDL would no longer be acceptingpatient samples for BRCA genetic testing.Myriad’s assertion of its patent rightsagainst Kazazian escalated into a patentinfringement suit by Myriad against theUniversity of Pennsylvania, which was la-ter dismissed without prejudice after theUniversity agreed to cease all accusedBRCA testing services. Myriad also suedOncormed for patent infringement basedon its BRCA genetic testing services. Asa result of Myriad’s patent enforcementactions, Dr. Ostrer was forced to send allpatient samples to Myriad, now the soleprovider of BRCA diagnostic testing ser-vices.

Dr. Ostrer, on the other hand, maintainsthat he could have proceeded with hisBRCA-related clinical activities withouttaking a license from Myriad. This asser-tion is based on his belief that the patentsMyriad claims cover such activities areinvalid because genes are patent-ineligibleproducts of nature. Acting on his belief,Ostrer seeks in this lawsuit a declarationof his right to undertake BRCA-relatedclinical activities without a license. Ac-cordingly, Myriad and Dr. Ostrer havetaken adverse legal positions regardingwhether or not Ostrer can engage inBRCA genetic testing without infringingany valid claim to ‘‘isolated’’ BRCA DNAsor methods of ‘‘analyzing’’ or ‘‘comparing’’BRCA sequences, as recited in Myriad’spatents. See Aetna Life, 300 U.S. at 242,57 S.Ct. 461 (holding declaratory judgmentjurisdiction existed when ‘‘the parties hadtaken adverse positions with respect totheir existing obligations’’ on an insurancecontract).

Dr. Ostrer has also alleged a controver-sy of sufficient reality and immediacy,MedImmune, 549 U.S. at 127, 127 S.Ct.


764; he has alleged a concrete and actualinjury traceable to Myriad’s assertion ofits patent rights, see Lujan, 504 U.S. at560, 112 S.Ct. 2130. First, Ostrer seeks toundertake specific BRCA-related activi-ties—BRCA diagnostic testing—for whichMyriad has demanded a license under spe-cific patents—those that cover the isolatedBRCA genes and BRCA diagnostic testing.Thus, Ostrer does not request ‘‘an opinionadvising what the law would be upon ahypothetical state of facts,’’ Aetna Life,300 U.S. at 241, 57 S.Ct. 461, but ratherwhether his proposed BRCA testing ser-vices are covered by valid patent claims to‘‘isolated’’ BRCA genes and methods of‘‘comparing’’ the genes’ sequences. Sec-ond, Ostrer not only has the resources andexpertise to immediately undertake clinicalBRCA testing, but also states unequivocal-ly that he will immediately begin suchtesting. In contrast to Ostrer, who allegesan actual and imminent injury for pur-poses of standing, Drs. Kazazian and Gan-guly allege only that they will ‘‘consider’’resuming BRCA testing. These ‘‘ ‘someday’ intentions’’ are insufficient to supportan ‘‘actual or imminent’’ injury for stand-ing ‘‘without TTT any specification of whenthe some day will be.’’ Lujan, 504 U.S. at564, 112 S.Ct. 2130. As a result, Drs.Kazazian and Ganguly do not have stand-ing.

[6] Myriad seeks to avoid this resultbased on the timing of its enforcementactions. Specifically, Myriad argues thattime has extinguished the immediacy andreality of any controversy, relying on lan-guage that hearkens back to our pre-Med-Immune reasonable apprehension of suittest. See, e.g., Appellants’ Br., 2010 WL4600106, at 26 (‘‘[A] patentee’s ten-year

silence presumptively extinguishes anyreasonable objective fear of suit.’’). Wedisagree. In many cases a controversymade manifest by a patentee’s affirmativeassertion of its patent rights will dissipateas market players and products change.In this case, however, the relevant circum-stances surrounding Myriad’s assertion ofits patent rights have not changed despitethe passage of time.8

Myriad’s active enforcement of its pat-ent rights forced Dr. Ostrer, as well asevery other similarly situated researcherand institution, to cease performing thechallenged BRCA testing services, leavingMyriad as the sole provider of BRCA clini-cal testing to patients in the United States.Since that time, neither the accused activi-ties nor the parties’ positions havechanged. First, Myriad does not allegethat genetic testing technology haschanged in any way that renders its pastassertions of its patent rights irrelevant toOstrer’s currently proposed BRCA testing.Rather, the patents cover, as Myriad as-serted in the late 1990s, the basic compo-nents of any such test: the isolated BRCAgenes and the diagnostic step of comparingthe genes’ sequences.

[7, 8] Second, ever since Myriad’s en-forcement efforts eliminated all competi-tion, Myriad and Ostrer have not alteredtheir respective positions. Ostrer, still la-boring under Myriad’s threat of infringe-ment liability, has not attempted to pro-vide BRCA testing; yet, as a researcher,he remains in the same position with re-spect to his ability and his desire to pro-vide BRCA testing as in the late 1990s.Furthermore, nothing in the record sug-gests that any researcher or institution has

8. Myriad’s analogy to laches is also uncon-vincing. Laches bars the recovery of pre-filing damages; it does not preclude a patentaction for prospective relief, the type of reliefsought here. See A.C. Aukerman Co. v. R.L.

Chaides Const. Co., 960 F.2d 1020, 1041 (Fed.Cir.1992) (en banc ) (‘‘[L]aches bars relief ona patentee’s claim only with respect to dam-ages accrued prior to suit.’’).


successfully attempted to compete withMyriad, or that Myriad has in any waychanged its position with regard to itspatent rights. Just as active enforcementof one’s patent rights against others canmaintain a real and immediate controversydespite the passage of time, see Micron,518 F.3d at 901, so too can the successfulassertion of such rights when the relevantcircumstances remain unchanged. Thus,consistent with the purpose of the Declara-tory Judgment Act, Ostrer need not riskliability and treble damages for patent in-fringement before seeking a declaration ofhis contested legal rights. See MedIm-mune, 549 U.S. at 134, 127 S.Ct. 764.

Myriad also argues that the record re-futes Ostrer’s claim that he has been re-strained from engaging in BRCA-relatedgene sequencing. Specifically, Myriad ar-gues that since Myriad published its dis-coveries of the BRCA1 and BRCA2 genesin October 1994 and March 1996, respec-tively, over 18,000 scientists have conduct-ed research on the BRCA genes and over8,600 research papers have been published.Furthermore, according to Myriad, plain-tiff Wendy Chung concedes that her labcurrently conducts sequencing of BRCAgenes. Yet, both Drs. Chung and Ostrerstate that, although they conduct gene se-quencing, they are forbidden from inform-ing their research subjects of the results oftheir BRCA tests without first sending thesamples to Myriad. Accordingly, Ostrer isrestrained from the BRCA-related activitythat he desires to undertake: clinical diag-nostic testing.

Myriad’s communications with Dr. Ostr-er confirm this understanding. The licens-ing letter Myriad sent to Ostrer proposeda collaborative agreement giving NYU theright to perform ‘‘Research Tests’’ withoutpayment to Myriad. J.A. 2967. ‘‘Re-search Tests’’ are defined as tests thatfurther ‘‘non-commercial research pro-grams, the results of which are not provid-

ed to the patient and for which no money isreceived.’’ J.A. 2965 (emphasis added).In contrast, the agreement requires pay-ment to Myriad for each ‘‘Testing Service’’performed, with ‘‘Testing Services’’ de-fined as ‘‘medical laboratory testing TTT

for the presence or absence of BRCA1mutations for the purpose of determiningor predicting predisposition to, or assess-ing the risk of breast or ovarian cancer inhumans.’’ J.A. 2966–67. Thus, Myriad’spatent enforcement actions never targetedthe non-clinical BRCA research now citedby Myriad, and Ostrer’s ability to performsuch research does not address the injuryasserted here.

[9] Finally, Myriad argued in its replybrief and at oral argument that Plaintiffs’declaratory action will not afford them therelief they want, a requirement for stand-ing. Lujan, 504 U.S. at 560–61, 112 S.Ct.2130; see also MedImmune, 549 U.S. at127 n. 7, 127 S.Ct. 764 (‘‘[A] litigant maynot use a declaratory-judgment action toobtain piecemeal adjudication of defensesthat would not finally and conclusivelyresolve the underlying controversy.’’).Specifically, Myriad asserts that becausePlaintiffs have challenged just fifteen com-position and method claims, while admit-ting that other unchallenged claims toBRCA probes and primers will still pre-vent them from engaging in BRCA se-quencing, a favorable decision will not re-dress the Plaintiffs’ alleged injury. Again,we disagree.

The Supreme Court has required onlythat it is ‘‘likely,’’ rather than ‘‘merely‘speculative,’ ’’ that the alleged injury willbe ‘‘redressed by a favorable decision.’’Lujan, 504 U.S. at 561, 112 S.Ct. 2130.The Court has not required certainty.For example, in Village of ArlingtonHeights v. Metropolitan Housing Develop-ment Corp., the Court held that the plain-tiffs had standing to challenge a suburb’s


exclusionary zoning ordinance, as the ordi-nance stood as ‘‘an absolute barrier’’ to thehousing development Metropolitan Hous-ing Development Corp. (‘‘MHDC’’) hadcontracted to provide in the village. 429U.S. 252, 261, 97 S.Ct. 555, 50 L.Ed.2d 450(1977). The Court noted that injunctiverelief, while removing the ‘‘barrier’’ of theordinance, would not ‘‘guarantee’’ that thehousing would be built since MHDC stillhad to secure financing, qualify for federalsubsidies, and carry through with con-struction. Id. The Court nevertheless rec-ognized that ‘‘all housing developments aresubject to some extent to similar uncer-tainties,’’ and concluded that it was suffi-cient that there was a ‘‘substantial proba-bility’’ that the housing development wouldbe built. Id. at 261, 264, 97 S.Ct. 555.

In this case, Myriad’s challenged compo-sition and method claims undisputedly pro-vide ‘‘an absolute barrier’’ to Dr. Ostrer’sability to undertake BRCA diagnostic test-ing activities, and a declaration of thoseclaims’ invalidity would remove that barri-er. See id. at 261, 97 S.Ct. 555. More-over, while there may be other patentclaims directed to BRCA probes and prim-ers that prevent Ostrer from performingBRCA diagnostic testing free of infringe-ment liability, Myriad has failed to directus to any specific unchallenged claim thatwill have that effect. And Plaintiffs’ coun-sel stated at the first oral argument in thiscase that his clients can sequence theBRCA genes without using BRCA probesand primers. Oral Arg. at 34:07–25,34:53–35:29 available at http://www.cafc.uscourts.gov/oral–argument–recordings/2010–1406/all. Accordingly, we decline toconstrue the asserted claims and decline tohold on this record that Dr. Ostrer’s pro-posed BRCA-related activities would in-fringe unchallenged claims to primers andprobes. We thus conclude that it is likely,not merely speculative, that Dr. Ostrer’sinjury will be redressed by a favorabledecision.

[10, 11] Although we affirm the districtcourt’s decision to exercise declaratoryjudgment jurisdiction over this case, we doso on narrower grounds. The districtcourt failed to limit its jurisdictional hold-ing to affirmative acts by the patenteedirected at specific Plaintiffs, see SanDisk,480 F.3d at 1380–81, erroneously holdingall the Plaintiffs had standing based on‘‘the widespread understanding that onemay engage in BRCA1/2 testing at the riskof being sued for infringement liability byMyriad,’’ DJ Op., 669 F.Supp.2d at 390.We disagree, and thus we reverse the dis-trict court’s holding that the various plain-tiffs other than Dr. Ostrer have standingto maintain this declaratory judgment ac-tion. Simply disagreeing with the exis-tence of a patent on isolated DNA se-quences or even suffering an attenuated,non-proximate, effect from the existence ofa patent does not meet the SupremeCourt’s requirement for an adverse legalcontroversy of sufficient immediacy andreality to warrant the issuance of a declar-atory judgment. See MedImmune, 549U.S. at 127, 127 S.Ct. 764. The variousorganizational plaintiffs in this suit in par-ticular were not the target of any enforce-ment action or offered license agreementsby Myriad and had made no preparation toundertake potentially infringing activities.They accordingly suffered no injury andthus lack standing to bring this action.See Prasco, 537 F.3d at 1338–42; CatTech, 528 F.3d at 880–81.

Having found one plaintiff with standingto maintain this declaratory judgment ac-tion, see Horne v. Flores, 557 U.S. 433, 129S.Ct. 2579, 2592–93, 174 L.Ed.2d 406(2009), we may turn now to the merits ofMyriad’s appeal of the district court’s sum-mary judgment decision, which held allfifteen challenged composition and methodclaims invalid under § 101.


II. Subject Matter Eligibility

[12] Under the Patent Act, ‘‘Whoeverinvents or discovers any new and usefulprocess, machine, manufacture, or compo-sition of matter, or any new and usefulimprovement thereof, may obtain a patenttherefor, subject to the conditions and re-quirements of this title.’’ 35 U.S.C. § 101.The Supreme Court has consistently con-strued § 101 broadly, explaining that ‘‘[i]nchoosing such expansive terms TTT modi-fied by the comprehensive ‘any,’ Congressplainly contemplated that the patent lawswould be given wide scope.’’ Bilski v.Kappos, ––– U.S. ––––, 130 S.Ct. 3218,3225, 177 L.Ed.2d 792 (2010) (quotingChakrabarty, 447 U.S. at 308, 100 S.Ct.2204).

[13] The Supreme Court, however, hasalso consistently held that § 101, althoughbroad, is not unlimited. Id. The Court’sprecedents provide three judicially createdexceptions to § 101’s broad patent-eligibili-ty principles: ‘‘ ‘Laws of nature, naturalphenomena, and abstract ideas’ are notpatentable.’’ Mayo, 132 S.Ct. at 1293(quoting Diamond v. Diehr, 450 U.S. 175,185, 101 S.Ct. 1048, 67 L.Ed.2d 155 (1981)).The Court has also referred to those ex-ceptions as precluding the patenting ofmental processes, Gottschalk v. Benson,409 U.S. 63, 67, 93 S.Ct. 253, 34 L.Ed.2d273 (1972), and products of nature, Chak-rabarty, 447 U.S. at 313, 100 S.Ct. 2204(‘‘[T]he relevant distinction for purposes of§ 101 is TTT between products of natureTTT and human-made inventions.’’). TheCourt has explained that, although not re-quired by the statutory text, ‘‘[t]he con-cepts covered by these exceptions are ‘partof the storehouse of knowledge of all menTTT free to all men and reserved exclusive-ly to none.’ ’’ Bilski, 130 S.Ct. at 3225(quoting Funk Bros. Seed Co. v. Kalo Ino-culant Co., 333 U.S. 127, 130, 68 S.Ct. 440,92 L.Ed. 588 (1948)).

[14] Plaintiffs challenge under § 101Myriad’s composition claims directed to‘‘isolated’’ DNA molecules, its methodclaims directed to ‘‘analyzing’’ or ‘‘compar-ing’’ DNA sequences, and its claim to amethod for screening potential cancertherapeutics. We address each in turn.Before reviewing the applicability of theSupreme Court’s Mayo holding to theclaims of the Myriad patents, however, it isimportant to state what this appeal is notabout. It is not about whether individualssuspected of having an increased risk ofdeveloping breast cancer are entitled to asecond opinion. Nor is it about whetherthe University of Utah, the owner of theinstant patents, or Myriad, the exclusivelicensee, has acted improperly in its licens-ing or enforcement policies with respect tothe patents. The question is also notwhether is it desirable for one company tohold a patent or license covering a testthat may save people’s lives, or for othercompanies to be excluded from the marketencompassed by such a patent—that is thebasic right provided by a patent, i.e., toexclude others from practicing the patent-ed subject matter. It is also not whetherthe claims at issue are novel or nonobviousor too broad. Those questions are notbefore us. It is solely whether the claimsto isolated BRCA DNA, to methods forcomparing DNA sequences, and to a pro-cess for screening potential cancer thera-peutics meet the threshold test for patent-eligible subject matter under 35 U.S.C.§ 101 in light of various Supreme Courtholdings, particularly including Mayo. Theissue is patent eligibility, not patentability.

We would further note, in the context ofdiscussing what this case is not about, thatpatents on life-saving material and pro-cesses, involving large amounts of riskyinvestment, would seem to be precisely thetypes of subject matter that should besubject to the incentives of exclusiverights. But disapproving of patents on


medical methods and novel biological mole-cules are policy questions best left to Con-gress, and other general questions relatingto patentability and use of patents areissues not before us. As will be seen, onthe limited questions before us, we con-clude that the composition claims and thescreening claim involving growing a trans-formed host cell meet the standards forpatent eligibility, while the claimed meth-ods for ‘‘analyzing’’ or ‘‘comparing’’ do not.

A. Composition Claims: IsolatedDNA Molecules

i.

The principal claims of the patents be-fore us on remand relate to isolated DNAmolecules. Mayo does not control thequestion of patent-eligibility of suchclaims. They are claims to compositions ofmatter, expressly authorized as suitablepatent-eligible subject matter in § 101.As to those claims, the issue of patent-eligibility remains, as it was on the firstappeal to this court, whether they claimpatent-ineligible products of nature. Wehold that they do not. The isolated DNAmolecules before us are not found in na-ture. They are obtained in the laboratoryand are man-made, the product of humaningenuity. While they are prepared fromproducts of nature, so is every other com-position of matter. All new chemical orbiological molecules, whether made by syn-thesis or decomposition, are made fromnatural materials. For example, virtuallyevery medicine utilized by today’s medicalpractitioners, and every manufacturedplastic product, is either synthesized fromnatural materials (most often petroleumfractions) or derived from natural plantmaterials. But, as such, they are differentfrom natural materials, even if they areultimately derived from them. The sameis true of isolated DNA molecules.

ii.

Myriad argues that its challenged com-position claims to ‘‘isolated’’ DNAs coverpatent-eligible compositions of matterwithin the meaning of § 101. According toMyriad, the district court came to a con-trary conclusion by (1) misreading Su-preme Court precedent as excluding frompatent eligibility all ‘‘products of nature’’unless ‘‘markedly different’’ from naturallyoccurring ones; and (2) incorrectly focus-ing not on the differences between isolatedand native DNAs, but on one similarity:their informational content. Rather, Myri-ad argues, an isolated DNA molecule ispatent eligible because it is, as claimed, ‘‘anonnaturally occurring manufacture orcomposition of matter’’ with ‘‘a distinctivename, character, and use.’’ Appellants’Br., 2010 WL 4600106, at 41–42 (quotingChakrabarty, 447 U.S. at 309–10, 100 S.Ct.2204). Myriad contends that isolatedDNA does not exist in nature and thatisolated DNAs, unlike native DNAs, can beused as primers and probes for diagnosingcancer. Moreover, Myriad asserts that anultimately-derived-from ‘‘products of na-ture’’ exception not only would be unwork-able, as every composition of matter is, atsome level, composed of natural materials,but also would be contrary to this court’sprecedents, the PTO’s 2001 Utility Exami-nation Guidelines, and Congress’s role inenacting the patent laws. RegardingMayo, Myriad argues that the SupremeCourt’s decision did not address or alterthe established patent-eligibility test forcomposition claims, such that the stan-dards announced in Chakrabarty still gov-ern this appeal. To the extent that thegeneral principles discussed in Mayo bearon the DNA claims, Myriad maintains thatisolated DNA represents a nonnatural,man-made invention distinct from the lackof human ingenuity underlying the methodclaims there at issue.


Plaintiffs respond that claims to isolatedDNA molecules fail to satisfy § 101 be-cause such claims cover natural phenome-na and products of nature. According toPlaintiffs, Supreme Court precedent estab-lishes that a product of nature is not pat-ent eligible even if, as claimed, it has un-dergone some highly useful change fromits natural form. Rather, Plaintiffs assert,to be patent eligible a composition of mat-ter must also have a distinctive name,character, and use, making it ‘‘markedlydifferent’’ from the natural product. Inthis case, Plaintiffs conclude that becauseisolated DNAs retain part of the samenucleotide sequence as native DNAs, theydo not have any ‘‘markedly different’’ char-acteristics. Furthermore, according toPlaintiffs, the isolated DNA claimspreempt products and laws of nature, ex-cluding anyone from working with theBRCA genes and the genetic informationthey convey. Under Mayo, Plaintiffs as-sert that any structural differences rela-tive to the chromosomal BRCA genes donot add ‘‘enough’’ to the underlying naturalgenetic sequences to render Myriad’s iso-lated DNA molecules patentable under§ 101.

The government as amicus curiae doesnot defend the longstanding position of thePTO, a government agency, that isolatedDNA molecules are patent eligible, argu-ing instead for a middle ground. Specifi-cally, the government argues that DNAmolecules engineered by man, includingcDNAs,9 are patent-eligible compositionsof matter because, with rare exceptions,they do not occur in nature, either in iso-lation or as contiguous sequences within achromosome. In contrast, the governmentasserts, isolated and unmodified genomicDNAs are not patent eligible, but rather

patent-ineligible products of nature, sincetheir nucleotide sequences exist because ofevolution, not man.

At the first oral argument, the govern-ment illustrated its position by way of a so-called ‘‘magic microscope’’ test (an inven-tion in and of itself, although probably notpatent-eligible). Oral Arg. at 46:50–47:50.According to the government’s test then, ifan imaginary microscope could focus in onthe claimed DNA molecule as it exists inthe human body, the claim covers ineligiblesubject matter. The government thus ar-gued that because such a microscope couldfocus in on the claimed isolated BRCA1 orBRCA2 sequences as they exist in thehuman body, the claims covering thosesequences are not patent eligible. In con-trast, the government contended, becausean imaginary microscope could not focusin vivo on a cDNA sequence, which isengineered by man to splice together non-contiguous coding sequences (i.e., exons),claims covering cDNAs are patent eligible.

In sum, although the parties and thegovernment appear to agree that isolatedDNAs are compositions of matter, theydisagree on whether and to what degreesuch molecules fall within the exception forproducts of nature. As set forth below, weconclude that the challenged claims to iso-lated DNAs, whether limited to cDNAs ornot, are directed to patent-eligible subjectmatter under § 101.

iii.

While Mayo and earlier decisions con-cerning method claim patentability providevaluable insights and illuminate broad,foundational principles, the SupremeCourt’s decisions in Chakrabarty andFunk Brothers set out the primary frame-work for deciding the patent eligibility ofcompositions of matter, including isolatedDNA molecules.10

9. According to the government, several of thecomposition claims at issue in this suit, in-cluding claim 2 of the 8282 patent, are limitedto cDNA and thus patent eligible. We agree.

10. Other Supreme Court decisions cited bythe parties and amici relating to patentedmanufactures and compositions of matterwere decided based on lack of novelty, not


In Chakrabarty, the Court addressedthe question whether a man-made, livingmicroorganism is a patent-eligible manu-facture or composition of matter within themeaning of § 101. 447 U.S. at 305, 307,100 S.Ct. 2204. The microorganisms werebacteria genetically engineered with fournaturally occurring DNA plasmids, each ofwhich enabled the breakdown of a differ-ent component of crude oil. Id. at 305, 305n. 1, 100 S.Ct. 2204. The bacteria, as aresult, could break down multiple compo-nents of crude oil, a trait possessed by nosingle naturally occurring bacterium andof significant use in more efficiently treat-ing oil spills. Id. at 305, 305 n. 2, 100 S.Ct.2204. The Court held that the bacteriaqualified as patent-eligible subject matterbecause the ‘‘claim is not to a hithertounknown natural phenomenon, but to anon-naturally occurring manufacture orcomposition of matter—a product of hu-man ingenuity ‘having a distinctive name,character [and] use.’ ’’ Id. at 309–10, 100S.Ct. 2204 (quoting Hartranft v. Wieg-mann, 121 U.S. 609, 615, 7 S.Ct. 1240, 30L.Ed. 1012 (1887)).

To underscore the point, the Court com-pared Chakrabarty’s engineered bacteriawith the mixed bacterial cultures foundunpatentable in Funk Brothers, again cast-ing this case, more relating to obviousness,in terms of § 101. See Parker v. Flook,437 U.S. 584, 591, 98 S.Ct. 2522, 57L.Ed.2d 451 (1978); Benson, 409 U.S. at

67, 93 S.Ct. 253. In Funk Brothers, thepatentee discovered that certain strains ofnitrogen-fixing bacteria associated with le-guminous plants do not mutually inhibiteach other. 333 U.S. at 129–30, 68 S.Ct.440. Based on that discovery, the paten-tee produced (and claimed) mixed culturesof nitrogen-fixing species capable of inocu-lating a broader range of leguminousplants than single-species cultures. Id.The Court held that the bacteria’s coopera-tive qualities were, ‘‘like the heat of thesun, electricity, or the qualities of metals,’’the ‘‘work of nature,’’ and thus not patent-able. Id. at 130, 68 S.Ct. 440. The Courtalso held that applying the newly discover-ed bacterial compatibility to create amixed culture was not a patentable ad-vance because no species acquired a differ-ent property or use. Id. at 131, 68 S.Ct.440. The Chakrabarty Court thus con-cluded that what distinguished Chakrabar-ty’s oil-degrading bacteria from the mixedcultures claimed in Funk Brothers, andmade the former patent-eligible, was thatChakrabarty’s bacteria had ‘‘markedly dif-ferent characteristics from any [bacterium]found in nature’’ based on the efforts ofthe patentee. Chakrabarty, 447 U.S. at310, 100 S.Ct. 2204.

One distinction, therefore, betweenproducts of nature and human-made in-vention for purposes of § 101 turns on achange in the claimed composition’s identi-

patent-eligible subject matter. In AmericanWood–Paper Co. v. Fibre Disintegrating Co.,the Court held the challenged patent ‘‘void forwant of novelty in the manufacture patented,’’because the ‘‘[p]aper-pulp obtained from vari-ous vegetable substances was in common usebefore the original patent was granted TTT,and whatever may be said of their process forobtaining it, the product was in no sensenew.’’ 90 U.S. 566, 596, 23 Wall. 566, 23L.Ed. 31 (1874). Similarly, in Cochrane v.Badische Anilin & Soda Fabrik, the Court heldthat a claim to artificial alizarine covered anold and well-known substance, the alizarine

of madder, which could not be patented al-though made artificially for the first time.111 U.S. 293, 311, 4 S.Ct. 455, 28 L.Ed. 433(1884); see also id. at 308–09, 4 S.Ct. 455 (‘‘Itis very plain that the specification of the origi-nal patent, No. 95,465, states the invention tobe a process for preparing alizarine, not as anew substance prepared for the first time, butas the substance already known as alizarine,to be prepared, however, by the new process,which process is to be the subject of thepatent, and is the process of preparing theknown product alizarine from anthracine.’’(emphases added)).


ty compared with what exists in nature.Specifically, the Supreme Court hasdrawn a line between compositions that,even if arrayed in useful combinations orharnessed to exploit newly discoveredproperties, have similar characteristics asin nature, and compositions that humanintervention has given ‘‘markedly differ-ent,’’ or ‘‘distinctive,’’ characteristics. Id.(citing Hartranft, 121 U.S. at 615, 7 S.Ct.1240); see also Am. Fruit Growers v.Brogdex Co., 283 U.S. 1, 11, 51 S.Ct. 328,75 L.Ed. 801 (1931). Applying this test tothe isolated DNAs in this case, the chal-lenged claims are drawn to patent-eligiblesubject matter because the claims covermolecules that are markedly different—have a distinctive chemical structure andidentity—from those found in nature.

It is undisputed that Myriad’s claimedisolated DNAs exist in a distinctive chemi-cal form—as distinctive chemical mole-cules—from DNAs in the human body, i.e.,native DNA. Natural DNA exists in thebody as one of forty-six large, contiguousDNA molecules. Each of those DNA mol-ecules is condensed and intertwined withvarious proteins, including histones, toform a complex tertiary structure knownas chromatin that makes up a larger struc-tural complex, a chromosome. See supra,Figure 3. Inside living cells, the chromo-somes are further encapsulated within aseries of membranes and suspended in acomplex intracellular milieu.

Isolated DNA, in contrast, is a free-standing portion of a larger, natural DNAmolecule. Isolated DNA has been cleaved(i.e., had covalent bonds in its backbonechemically severed) or synthesized to con-sist of just a fraction of a naturally occur-ring DNA molecule. For example, theBRCA1 gene in its native state resides onchromosome 17, a DNA molecule ofaround eighty million nucleotides. Simi-larly, BRCA2 in its native state is locatedon chromosome 13, a DNA of approximate-

ly 114 million nucleotides. In contrast,isolated BRCA1 and BRCA2, with introns,each consists of just 80,000 or so nucleo-tides. And without introns, BRCA2shrinks to approximately 10,200 nucleo-tides and BRCA1 to just around 5,500nucleotides. Furthermore, claims 5 and 6of the 8282 patent cover isolated DNAs,e.g., primers or probes, having as few asfifteen nucleotides of a BRCA sequence.Accordingly, BRCA1 and BRCA2 in theirisolated states are different moleculesfrom DNA that exists in the body; isolatedDNA results from human intervention tocleave or synthesize a discrete portion of anative chromosomal DNA, imparting onthat isolated DNA a distinctive chemicalidentity as compared to native DNA.

As the above description indicates, iso-lated DNA is not just purified DNA. Puri-fication makes pure what was the samematerial, but was combined, or contaminat-ed, with other materials. Although isolat-ed DNA is removed from its native cellularand chromosomal environment, it has alsobeen manipulated chemically so as to pro-duce a molecule that is markedly differentfrom that which exists in the body. Ac-cordingly, this is not a situation, as inParke–Davis & Co. v. H.K. Mulford Co., inwhich purification of adrenaline resulted inthe identical molecule, albeit being ‘‘forevery practical purpose a new thing com-mercially and therapeutically.’’ 189 F. 95,103 (C.C.S.D.N.Y.1911). Judge LearnedHand’s opinion for the district court in thatoft-cited case held the purified ‘‘Adrenalin’’to be patent-eligible subject matter. Id.The In re Marden cases are similarly inap-posite, directed as they are to the patentineligibility of purified natural elements—ductile uranium, 18 CCPA 1046, 47 F.2d957 (1931), and vanadium, 18 CCPA 1057,47 F.2d 958 (1931)—that are inherentlyductile in purified form. While purifiednatural products thus may or may notqualify for patent under § 101, the isolated


DNAs of the present patents constitute ana fortiori situation, where they are notonly purified; they are different from thenatural products in ‘‘name, character, anduse.’’ Chakrabarty, 447 U.S. at 309–10,100 S.Ct. 2204.11

Parke–Davis and Marden address a sit-uation in which claimed compound A ispurified from a physical mixture that con-tains compound A. In this case, theclaimed isolated DNA molecules do notexist in nature within a physical mixture tobe purified. They have to be chemicallycleaved from their native chemical combi-nation with other genetic materials. Inother words, in nature, the claimed isolat-ed DNAs are covalently bonded to suchother materials. Thus, when cleaved, anisolated DNA molecule is not a purifiedform of a natural material, but a distinctchemical entity that is obtained by humanintervention. See Chakrabarty, 447 U.S.at 313, 100 S.Ct. 2204 (‘‘the relevant dis-tinction [is] between products of natureTTT and human-made inventions’’). Infact, some forms of isolated DNA mayrequire no purification at all, becauseDNAs can be chemically synthesized di-rectly as isolated molecules.

[15] The above analysis holding theisolated DNA molecules to be patent-eligi-

ble subject matter applies to all of theasserted composition claims on appeal inthis case. However, as the governmenthas pointed out, claim 2 of the 8282 patentis narrower than claim 1 and reads onlyon cDNAs, which lack the non-coding in-trons present in the genomic BRCA1gene.12 While, as we have held, all of theclaimed isolated DNAs are eligible for pat-ent as compositions of matter distinctfrom natural DNA, the claimed cDNAsare especially distinctive, lacking the non-coding introns present in naturally occur-ring chromosomal DNA. They are evenmore the result of human intervention intonature and are hence patent-eligible sub-ject matter. The government, as notedearlier, has agreed with that conclusion.Br. United States, 2010 WL 4853320, at14–17.

The dissent disparages the significanceof a ‘‘chemical bond,’’ presumably meaninga covalent bond, in distinguishing structur-ally between one molecular species andanother. But a covalent bond is the defin-ing boundary between one molecule andanother, and the dissent’s citation of LinusPauling’s comment that covalent bonds‘‘make it convenient for the chemist toconsider [the aggregate] as an independentmolecular species’’ underlines the point.

11. In re Bergy, relating to a purified microor-ganism, 596 F.2d 952, 967–68 (CCPA 1979),was once a companion case to Chakrabartybut was vacated by the Supreme Court andremanded for dismissal as moot when theinventors withdrew their claim from thepending application. Diamond v. Chakrabar-ty, 444 U.S. 1028, 100 S.Ct. 696, 62 L.Ed.2d664 (1980). Other CCPA cases cited by theparties and amici were not decided based onpatent eligibility. In In re Bergstrom, thecourt held that pure prostaglandin com-pounds, PGE(2) and PGE(3), were improperlyrejected as lacking novelty. 57 CCPA 1240,427 F.2d 1394, 1394 (1970); see Bergy, 596F.2d at 961 (recognizing Bergstrom as a casedecided under § 102). Similarly in In reKratz, the court held nonobvious claims to

synthetically produced, substantially pure 2–methyl–2–pentenoic acid, a chemical thatgives strawberries their flavor. 592 F.2d1169, 1170 (CCPA 1979); see also In re King,27 CCPA 754, 107 F.2d 618, 619 (1939) (hold-ing claims to vitamin C invalid for lack ofnovelty, as ‘‘[a]ppellants were not the first todiscover or produce [vitamin C] in its pureform’’); In re Merz, 25 CCPA 1314, 97 F.2d599, 601 (1938) (holding claims to artificialultramarine that contains non-floatable impu-rities invalid as not ‘‘inventive,’’ and thusobvious).

12. Claims 2 and 7 of the 8282 patent andclaim 7 of the 8492 patent recite isolatedcDNA molecules.


The covalent bonds in this case connectdifferent chemical moieties to one another.

[16, 17] Plaintiffs argue that becausethe claimed isolated DNAs retain the samenucleotide sequence as native DNAs, theydo not have any ‘‘markedly different’’ char-acteristics. This approach, however, looksnot at whether isolated DNAs are marked-ly different—have a distinctive characteris-tic—from naturally occurring DNAs, asthe Supreme Court has directed, but atone similarity, albeit a key one: the infor-mation content contained in isolated andnative DNAs’ nucleotide sequences.Adopting this approach, the district courtdisparaged the patent eligibility of isolatedDNA molecules because their genetic func-tion is to transmit information. We dis-agree, as it is the distinctive nature ofDNA molecules as isolated compositions ofmatter that determines their patent eligi-bility rather than their physiological use orbenefit. Uses of chemical substances maybe relevant to the nonobviousness of thesesubstances or to method claims embodyingthose uses, but the patent eligibility of anisolated DNA is not negated because it hassimilar informational properties to a differ-ent, more complex natural material. Theclaimed isolated DNA molecules are dis-tinct from their natural existence as por-tions of larger entities, and their informa-tional content is irrelevant to that fact.We recognize that biologists may think ofmolecules in terms of their uses, but genesare in fact materials having a chemicalnature and, as such, are best described inpatents by their structures rather than bytheir functions. In fact, many differentmaterials may have the same function (e.g.,aspirin, ibuprofen, and naproxen).

The district court in effect created acategorical rule excluding isolated genesfrom patent eligibility. See SJ Op., 702F.Supp.2d at 228–29. But the SupremeCourt has ‘‘more than once cautioned thatcourts ‘should not read into the patent

laws limitations and conditions which thelegislature has not expressed,’ ’’ Bilski, 130S.Ct. at 3226 (quoting Diehr, 450 U.S. at182, 101 S.Ct. 1048), and has repeatedlyrejected new categorical exclusions from§ 101’s scope, see id. at 3227–28 (rejectingthe argument that business method pat-ents should be categorically excluded from§ 101); Chakrabarty, 447 U.S. at 314–17,100 S.Ct. 2204 (same for living organisms).Contrary to the conclusions of the districtcourt and the suggestions of Plaintiffs andsome amici, § 101 applies equally to allputative inventions, and isolated DNA isnot and should not be considered a specialcase for purposes of patent eligibility un-der existing law. See, e.g., SJ Op., 702F.Supp.2d at 185 (‘‘DNA represents thephysical embodiment of biological informa-tion, distinct in its essential characteristicsfrom any other chemical found in na-ture.’’); Appellees’ Suppl. Br. at 4–5(‘‘Unlike other chemicals, the informationencoded by DNA reflects its primary bio-logical functionTTTT’’).

Under the statutory rubric of § 101, iso-lated DNA is a tangible, man-made compo-sition of matter defined and distinguishedby its objectively discernible chemicalstructure. Whether its unusual status asa chemical entity that conveys genetic in-formation warrants singular treatment un-der the patent laws as the district courtdid is a policy question that we are notentitled to address. Cf. Nat’l Fed’n ofIndep. Bus. v. Sebelius, ––– U.S. ––––, 132S.Ct. 2566, 2579, 183 L.Ed.2d 450 (2012)(‘‘[W]e possess neither the expertise northe prerogative to make policy judgments.Those decisions are entrusted to our Na-tion’s elected leaders, who can be thrownout of office if the people disagree withthem.’’). Congress is presumed to havebeen aware of the issue, having enacted acomprehensive patent reform act duringthe pendency of this case, and it is ulti-mately for Congress if it wishes to over-


turn case law and the long practice of thePTO to determine that isolated DNA mustbe treated differently from other composi-tions of matter to account for its perceivedspecial function. We therefore reject thedistrict court’s unwarranted categorical ex-clusion of isolated DNA molecules.

Because isolated DNAs, not just cDNAs,have a markedly different chemical struc-ture compared to native DNAs, we rejectthe government’s earlier proposed ‘‘magicmicroscope’’ test, as it misunderstands thedifference between science and inventionand fails to take into account the existenceof molecules as separate chemical entities.The ability to visualize a DNA moleculethrough a microscope, or by any othermeans, when it is bonded to other geneticmaterial, is worlds apart from possessingan isolated DNA molecule that is in handand usable. It is the difference betweenknowledge of nature and reducing a por-tion of nature to concrete form, the latteractivity being what the patent laws seek toencourage and protect. The government’smicroscope could focus in on a claimedportion of any complex molecule, render-ing that claimed portion patent ineligible,even though that portion never exists as aseparate molecule in the body or anywhereelse in nature, and may have an entirelydifferent utility. That would discourageinnovation. One cannot visualize a portionof a complex molecule, including a DNAcontaining a particular gene, and will itinto isolation as a unique entity. Visual-ization does not cleave and isolate the par-ticular DNA; that is the act of humaninvention.

The Supreme Court in Mayo focused onits concern that permitting patents on par-ticular subject matter would prevent useby others of, in Mayo, the correlation re-

cited in the method claims. Plaintiffs arguehere that they are preempted from usingthe patented DNA molecules. The answerto that concern is that permitting patentson isolated genes does not preempt a lawof nature. A composition of matter is nota law of nature. Moreover, as indicatedearlier, a limited preemption is inherent inevery patent: the right to exclude for alimited period of time. 35 U.S.C.§ 154(a)(1) (‘‘Every patent shall containTTT a grant to the patentee, his heirs orassigns, of the right to exclude others frommaking, using, offering for sale, or sellingthe invention throughout the UnitedStatesTTTT’’). When the patent expires,the public is entitled to practice the inven-tion of the patent. That is true of allinventions; during the term of the patent,unauthorized parties are ‘‘preempted’’from practicing the patent, but only for itslimited term. The seven patents beingchallenged here all expire by December 18,2015.13 Any preemption thus is limited,very limited in the case of the presentpatents. Moreover, patents are rarely en-forced against scientific research, evenduring their terms.

The remand of this case for reconsidera-tion in light of Mayo might suggest, asPlaintiffs and certain amici state, that thecomposition claims are mere reflections ofa law of nature. Respectfully, they arenot, any more than any product of manreflects and is consistent with a law ofnature. Everything and everyone comesfrom nature, following its laws. But thecompositions here are not natural prod-ucts. They are the products of man, albeitfollowing, as all materials do, laws of na-ture.

13. Specifically, the 8441 patent will expire onAugust 12, 2014; the 8473 patent will expireon December 2, 2014; the 8999 and 8001patents will expire on January 20, 2015; the

8282 patent will expire on May 5, 2015; andthe 8492 and 8857 patents will expire on De-cember 18, 2015.


The dissent indicates that ‘‘elemental li-thium (like other elements) would not bepatentable subject matter, even if it couldonly be extracted from nature through anisolation process.’’ But the isolation hereis not a simple separation from extraneousmaterials, but conversion to a differentmolecular entity. And again, these factsare not before us, so we do not attempt toevaluate the patentability of one form oflithium over another. Courts decide cases;they do not draft comprehensive legaltreatises. Suffice it to say, however, that iflithium is found in the earth as other thanelemental lithium because it reacts with airand water to form, for example, lithiumoxide or lithium hydroxide, it is a differentmaterial. A lithium compound is not ele-mental lithium.

[18] It is also important to dispute thedissent’s analogy to snapping a leaf from atree. With respect, no one could contem-plate that snapping a leaf from a treewould be worthy of a patent, whereas iso-lating genes to provide useful diagnostictools and medicines is surely what thepatent laws are intended to encourage andprotect. Snapping a leaf from a tree is aphysical separation, easily done by anyone.Creating a new chemical entity is the workof human transformation, requiring skill,knowledge, and effort. See Mayo, 132S.Ct. at 1294 (‘‘While a scientific truth TTT

is not a patentable invention, a novel anduseful structure created with the aid ofknowledge of scientific truth may be.’’)(quoting Mackay Radio & Tel. Co. v. Ra-dio Corp. of Am., 306 U.S. 86, 94, 59 S.Ct.427, 83 L.Ed. 506 (1939)).

The dissent also mentions several timesin its opinion the ‘‘breathtaking[ ]’’ breadthof certain claims as grounds for objectingto their patentability. However, we do nothave here any rejection or invalidation onthe various grounds relating to breadth,such as in 35 U.S.C. § 112. The issuebefore us is patent eligibility under § 101,

not the adequacy of the patents’ disclosureto support particular claims. Nor is it lackof patentability for obviousness, as the dis-sent intimates, that is before us.

The dissent finally attempts to analogizethe creation of the isolated DNAs in thiscase to the removal of a kidney from thehuman body, indicating that the latter doesnot create patent-eligible subject matter,hence the claimed isolated DNAs also donot. Such an analogy is misplaced. Ex-tracting a kidney from a body does notresult in a patent-eligible composition, asan isolated gene has been and should be.A kidney is an organ, not a well definedcomposition of matter or an article of man-ufacture specified by § 101. No one couldconfuse extensive research needed to lo-cate, identify, and isolate a gene with theextraction of an organ from a body. Oneis what patents are intended to stimulateresearch on and hence are properly patenteligible, and the other, while obviously es-sential to human wellbeing, is not whatpatents are understood to cover under thepatent statute. An isolated DNA is prop-erly characterized as a composition of mat-ter under § 101; no one would so charac-terize an isolated body organ.

Finally, our decision that isolated DNAmolecules are patent eligible comportswith the longstanding practice of thePTO and the courts. The SupremeCourt has repeatedly stated that changesto longstanding practice should comefrom Congress, not the courts. InJ.E.M. Ag Supply, Inc. v. Pioneer Hi–Bred International, Inc., the Court re-jected the argument that plants did notfall within the scope of § 101, relying inpart on the fact that ‘‘the PTO has as-signed utility patents for plants for atleast 16 years and there has been no in-dication from either Congress or agencieswith expertise that such coverage is in-consistent with [federal law].’’ 534 U.S.


124, 144–45, 122 S.Ct. 593, 151 L.Ed.2d508 (2001); see also Festo Corp. v. Shok-etsu Kinzoku Kogyo Kabushiki Co., 535U.S. 722, 739, 122 S.Ct. 1831, 152L.Ed.2d 944 (2002) (‘‘[C]ourts must becautious before adopting changes thatdisrupt the settled expectations of the in-venting community.’’ (citing Warner–Jen-kinson Co. v. Hilton Davis Chem. Co.,520 U.S. 17, 28, 117 S.Ct. 1040, 137L.Ed.2d 146 (1997))); Ariad Pharms.,Inc. v. Eli Lilly & Co., 598 F.3d 1336,1347 (Fed.Cir.2010) (en banc) (upholdinga written description requirement sepa-rate from enablement based in part onstare decisis ).

In this case, the PTO has issued patentsrelating to DNA molecules for almost thir-ty years. In the early 1980s, the Officegranted the first human gene patents. SeeEric J. Rogers, Can You Patent Genes?Yes and No, 93 J. Pat. & Trademark Off.Soc’y 19 (2010). It is estimated that thePTO has issued 2,645 patents claiming‘‘isolated DNA’’ over the past twenty-nineyears, J.A. 3710, and that by 2005, hadgranted 40,000 DNA-related patents relat-ing to, in non-native form, genes in thehuman genome, Rogers, supra at 40. In2001, the PTO issued Utility ExaminationGuidelines, which reaffirmed the agency’sposition that isolated DNA molecules arepatent eligible, 66 Fed.Reg. 1092–94 (Jan.5, 2001), and Congress has not indicatedthat the PTO’s position is inconsistent with§ 101. If the law is to be changed, andDNA inventions excluded from the broadscope of § 101, contrary to the settledexpectation of the inventing and investingcommunities, the decision must come, notfrom the courts, but from Congress. Thedissent mentions possible ‘‘adverse effects’’that may occur if isolated DNAs are heldto be patent eligible. But, respectfully, itis the adverse effects on innovation that aholding of ineligibility might cause. Pat-ents encourage innovation and even en-courage inventing around; we must be

careful not to rope off far-reaching areasof patent eligibility.

Accordingly, we once again concludethat claims 1, 2, 5, 6, and 7 of the 8282patent; claims 1, 6, and 7 of the 8492patent; and claim 1 of the 8473 patentdirected to isolated DNA molecules recitepatent-eligible subject matter under § 101.Mayo does not change that result. In sodoing, we reiterate that the issue before usis patent eligibility, not patentability,about which we express no opinion.

III. Method Claims

[19] We turn next to Myriad’s chal-lenged method claims. This court in itsnow-vacated decision of July 29, 2011, hadheld method claims 1 of the 8999, 8001, and8441 patents, as well as method claims 1and 2 of the 8857 patent—all of whichconsist of analyzing and comparing certainDNA sequences—not to be patent-eligiblesubject matter on the ground that theyclaim only abstract mental processes. Inlight of the Supreme Court’s decision inMayo, we reaffirm that prior holding.The Court made clear that such diagnosticmethods in that case essentially claim nat-ural laws that are not eligible for patent.Without expressly analyzing the instantmethod claims in the context of the Court’sreasoning, but in light of the Court’s hold-ing, and in view of our own prior reason-ing, set forth herein below, those methodclaims cannot stand.

In our prior decision, however, we re-versed the district court’s holding thatclaim 20 of the 8282 patent was not eligiblefor patent. We did so on the ground, interalia, that, in addition to the step of com-paring the cells’ growth rates, the claimalso recites the steps of growing trans-formed cells and determining those growthrates. We relied on the fact that thosesteps were transformative. Although theCourt has now held that certain transfor-


mative steps are not necessarily sufficientunder § 101 if the recited steps only relyon natural laws, we once again, even inlight of Mayo, arrive at the same conclu-sion of patent-eligibility because at theheart of claim 20 is a transformed cell,which is made by man, in contrast to anatural material.

A. Methods of ‘‘Comparing’’ or‘‘Analyzing’’ Sequences

Myriad argued that its claims to meth-ods of ‘‘comparing’’ or ‘‘analyzing’’ BRCAsequences satisfy the machine-or-transfor-mation test because each requires a trans-formation—extracting and sequencingDNA molecules from a human sample—before the sequences can be compared oranalyzed. According to Myriad, the dis-trict court failed to recognize the transfor-mative nature of the claims by (1) miscon-struing the claim term ‘‘sequence’’ asmerely information, rather than a physicalmolecule; and (2) erroneously concluding,in the alternative, that Myriad’s proposedtransformations were mere data-gatheringsteps, rather than central to the purpose ofthe claims.

Plaintiffs responded that these methodclaims are drawn to the abstract idea ofcomparing one sequence to a referencesequence and preempt a phenomenon ofnature—the correlation of genetic muta-tions with a predisposition to cancer. And,according to the Plaintiffs, limiting theclaims’ application to a specific technologi-cal field, i.e., BRCA gene sequences, isinsufficient to render the claims patenteligible. Plaintiffs also assert that theclaims do not meet the machine-or-trans-formation test because the claims’ plainlanguage includes just the one step of‘‘comparing’’ or ‘‘analyzing’’ two gene se-quences.

We renew our conclusion that Myriad’sclaims to ‘‘comparing’’ or ‘‘analyzing’’ twogene sequences fall outside the scope of

§ 101 because they claim only abstractmental processes. See Benson, 409 U.S. at67, 93 S.Ct. 253 (‘‘Phenomena of nature,TTT mental processes, and abstract intel-lectual concepts are not patentable, as theyare the basic tools of scientific and techno-logical work.’’). The claims recite, for ex-ample, a ‘‘method for screening a tumorsample,’’ by ‘‘comparing’’ a first BRCA1sequence from a tumor sample and a sec-ond BRCA1 sequence from a non-tumorsample, wherein a difference in sequenceindicates an alteration in the tumor sam-ple. 8001 patent claim 1. This claim thusrecites nothing more than the abstractmental steps necessary to compare twodifferent nucleotide sequences: one looksat the first position in a first sequence;determines the nucleotide sequence at thatfirst position; looks at the first position ina second sequence; determines the nucleo-tide sequence at that first position; deter-mines if the nucleotide at the first positionin the first sequence and the first positionin the second sequence are the same ordifferent, wherein the latter indicates analteration; and repeats the process for thenext position.

[20] Limiting the comparison to justthe BRCA genes or, as in the case of claim1 of the 8999 patent, to just the identifica-tion of particular alterations, fails to ren-der the claimed process patent-eligible.As the Supreme Court has held, ‘‘the pro-hibition against patenting abstract ideas‘cannot be circumvented by attempting tolimit the use of the formula to a particulartechnological environment.’ ’’ Bilski, 130S.Ct. at 3230 (quoting Diehr, 450 U.S. at191–92, 101 S.Ct. 1048); see also id. at3231 (‘‘Flook established that limiting anabstract idea to one field of use TTT did notmake the concept patentable.’’). Althoughthe application of a formula or abstractidea in a process may describe patent-eligible subject matter, id. at 3230, Myri-


ad’s claims do not apply the step of com-paring two nucleotide sequences in a pro-cess. Rather, the step of comparing twoDNA sequences is the entire process thatis claimed.

To avoid this result, Myriad attempts toread into its method claims additional, al-legedly transformative steps. As de-scribed above, Myriad reads into its claimsthe steps of (1) extracting DNA from ahuman sample, and (2) sequencing theBRCA DNA molecule, arguing that bothsteps necessarily precede the step of com-paring nucleotide sequences. The claimsthemselves, however, do not include eitherof these steps. The claims do not specifyany action prior to the step of ‘‘comparing’’or ‘‘analyzing’’ two sequences; the claimsrecite just the one step of ‘‘comparing’’ or‘‘analyzing.’’ Moreover, those terms’ plainmeaning does not include Myriad’s pro-posed sample-processing steps; neithercomparing nor analyzing means or implies‘‘extracting’’ or ‘‘sequencing’’ DNA or oth-erwise ‘‘processing’’ a human sample.

Myriad claims that ‘‘comparing’’ and‘‘analyzing’’ take on such meaning whenread in light of the patent specifications.Specifically, Myriad argues that the speci-fications show that the claim term ‘‘se-quence’’ refers not to information, butrather to a physical DNA molecule, whosesequence must be determined before it canbe compared. That may be true, but theclaims only recite mental steps, not thestructure of physical DNA molecules.

Accordingly, Myriad’s challenged meth-od claims are indistinguishable from theclaims the Supreme Court found invalidunder § 101 in Mayo. In Mayo, the pat-ents claimed methods for optimizing thedosage of thiopurine drugs administered topatients with gastrointestinal disorders.132 S.Ct. at 1295. As written, the claimedmethods included the steps of (a) ‘‘adminis-tering’’ a thiopurine drug to a subject,and/or (b) ‘‘determining’’ the drug’s meta-

bolite levels in the subject, wherein themeasured metabolite levels are comparedwith predetermined levels to optimize drugdosage. Id. In holding that the claimssatisfied § 101, this court concluded that,in addition to the ‘‘administering’’ step be-ing transformative, the ‘‘determining’’ stepwas both transformative and central to thepurpose of the claims. Prometheus, 628F.3d at 1357. However, the SupremeCourt held that the steps of administeringand determining, combined with a correla-tive ‘‘wherein’’ clause, were not sufficientlytransformative of what was otherwise aclaim to a natural law. That holding gov-erns Myriad’s claims to methods of ‘‘com-paring’’ and ‘‘analyzing’’ DNA sequences.

Myriad’s other claims do not even in-clude a Mayo-like step of ‘‘determining’’the sequence BRCA genes by, e.g., isolat-ing the genes from a blood sample andsequencing them, or any other putativelytransformative step. Rather, the compari-son between the two sequences can beaccomplished by mere inspection alone.Accordingly, Myriad’s claimed methods ofcomparing or analyzing nucleotide se-quences are only directed to the abstractmental process of comparing two nucleo-tide sequences. As such, we hold claims 1of the 8999 patent, 8001 patent, and 8441patent and claims 1 and 2 of the 8857patent invalid under § 101 for claimingpatent-ineligible processes.

B. Method of Screening PotentialCancer Therapeutics

[21] Lastly, we turn to claim 20 of the8282 patent, directed to a method forscreening potential cancer therapeutics viachanges in cell growth rates of trans-formed cells. The parties agree that thosetransformed cells arose from human effort;i.e., they are not natural products. Plain-tiffs nonetheless challenge claim 20 as di-rected to the abstract idea of comparing


the growth rates of two cell populationsand as preempting a basic scientific princi-ple—that a slower growth rate in the pres-ence of a potential therapeutic compoundsuggests that the compound is a cancertherapeutic. Plaintiffs therefore contendthat claim 20 is indistinguishable from theclaims held ineligible in Mayo. We dis-agree.

Claim 20 recites a method that compris-es the steps of (1) growing host cells trans-formed with an altered BRCA1 gene in thepresence or absence of a potential cancertherapeutic, (2) determining the growthrate of the host cells with or without thepotential therapeutic, and (3) comparingthe growth rate of the host cells. Claim 20thus recites a screening method premisedon the use of ‘‘transformed’’ host cells.Those cells, like the patent-eligible cells inChakrabarty, are not naturally occurring.Rather, they are derived by altering a cellto include a foreign gene, resulting in aman-made, transformed cell with enhancedfunction and utility. See 8282 patent col.2711.28–33. The claim thus includes morethan the abstract mental step of looking attwo numbers and ‘‘comparing’’ two hostcells’ growth rates.

In Mayo, the Supreme Court invalidatedclaims directed to the relationship betweenconcentrations of certain metabolites in theblood and the likelihood that a particulardosage of a thiopurine drug will be opti-mum, stating that steps of ‘‘administering’’and ‘‘determining,’’ coupled with a correla-tive ‘‘wherein’’ clause, were insufficient todifferentiate the claimed method from thenatural laws encompassed by the claims.In short, ‘‘to transform an unpatentablelaw of nature into a patent-eligible appli-cation of such a law, one must do morethan simply state the law of nature whileadding the words ‘apply it’.’’ 132 S.Ct. at1294.

Here, claim 20 does do more; it doesnot simply apply a law of nature. Ofcourse, all activity, whether chemical, bio-logical, or physical, relies on natural laws.But, more to the point here is that claim20 applies certain steps to transformedcells that, as has been pointed out above,are a product of man, not of nature. TheCourt, in its evaluation of the Mayo meth-od claims, found that the additional stepsof those claims were not sufficient to‘‘transform’’ the nature of the claims frommere expression of natural laws to patent-eligible subject matter. By definition,however, performing operations, evenknown types of steps, on, or to create,novel, i.e., transformed subject matter isthe stuff of which most process or methodinvention consists. All chemical processes,for example, consist of hydrolyzing, hydro-genating, reacting, etc. In situationswhere the objects or results of such stepsare novel and nonobvious, they should bepatent-eligible. It is rare that a new reac-tion or method is invented; much processactivity is to make new compounds orproducts using established processes.Thus, once one has determined that aclaimed composition of matter is patent-eligible subject matter, applying variousknown types of procedures to it is notmerely applying conventional steps to alaw of nature. The transformed, man-made nature of the underlying subjectmatter in claim 20 makes the claim patent-eligible. The fact that the claim also in-cludes the steps of determining the cells’growth rates and comparing growth ratesdoes not change the fact that the claim isbased on a man-made, non-naturally occur-ring transformed cell—patent-eligible sub-ject matter.

Furthermore, the claim does not coverall cells, all compounds, or all methods ofdetermining the therapeutic effect of acompound. Rather, it is tied to specifichost cells transformed with specific genes


and grown in the presence or absence ofa specific type of therapeutic. According-ly, we hold that claim 20 of the 8282 pat-ent recites patent-eligible subject matterunder § 101. Whether such processes,including claim 20, meet other tests forpatentability, such as novelty or nonobvi-ousness, is not before us.

CONCLUSION

For the foregoing reasons, we affirm thedistrict court’s decision to exercise declara-tory judgment jurisdiction over this case,we reverse the district court’s grant ofsummary judgment with regard to Myri-ad’s composition claims to isolated DNAs,including cDNAs, we affirm the districtcourt’s grant of summary judgment withregard to Myriad’s method claims directedto comparing or analyzing gene sequences,and we reverse the district court’s grant ofsummary judgment with regard to Myri-ad’s method claim to screening potentialcancer therapeutics via changes in cellgrowth rates of novel, man-made trans-formed cells.

AFFIRMED IN PART and RE-VERSED IN PART

COSTS

Costs to Myriad.

MOORE, Circuit Judge, concurring inpart.

I join the majority opinion with respectto standing and the patentability of themethod claims at issue. I join the majori-ty with respect to claims to isolated cDNAsequences, and concur in the judgmentwith respect to isolated DNA sequences.I write separately to explain my reasoning.

I.

The Patent Act, 35 U.S.C. § 101, allows‘‘[w]hoever invents or discovers any new

and useful process, machine, manufacture,or composition of matter, or any new anduseful improvement thereof’’ to obtain apatent. The plain language of this statuteonly requires that an invention be ‘‘newand useful,’’ and fall into one of four cate-gories: a ‘‘process, machine, manufacture,or composition of matter.’’ ‘‘Congress in-tended statutory subject matter to ‘includeanything under the sun that is made byman.’ ’’ Diamond v. Chakrabarty, 447 U.S.303, 309, 100 S.Ct. 2204, 65 L.Ed.2d 144(1980) (quoting the statutory history).

While the plain language used by Con-gress did not limit the scope of patentablesubject matter in the statute, the ‘‘Court’sprecedents provide three specific excep-tions to § 101’s broad patent-eligibilityprinciples: ‘laws of nature, physical phe-nomena, and abstract ideas.’ ’’ Bilski v.Kappos, ––– U.S. ––––, 130 S.Ct. 3218,3226, 177 L.Ed.2d 792 (2010) (quotingChakrabarty, 447 U.S. at 309, 100 S.Ct.2204). These exceptions ‘‘rest[ ], not onthe notion that natural phenomena are notprocesses [or other articulated statutorycategories], but rather on the more funda-mental understanding that they are notthe kind of ‘discoveries’ that the statutewas enacted to protect.’’ Parker v. Flook,437 U.S. 584, 593, 98 S.Ct. 2522, 57L.Ed.2d 451 (1978).

Applying the judicially created excep-tion to the otherwise broad demarcationof statutory subject matter in section 101can be difficult. See Funk Bros. Seed Co.v. Kalo Inoculant Co., 333 U.S. 127, 134–35, 68 S.Ct. 440, 92 L.Ed. 588 (1948)(Frankfurter, J., concurring) (‘‘[S]uchterms as ‘the work of nature’ and the‘laws of nature’ TTT are vague and mallea-bleTTTT Arguments drawn from suchterms for ascertaining patentability couldfairly be employed to challenge almost ev-ery patent.’’). The analysis is relativelysimple if the invention previously existed


in nature exactly as claimed. For exam-ple, naturally existing minerals, a plantfound in the wild, and physical laws suchas gravity or E=mc 2 are not patentablesubject matter, even if they were ‘‘discov-ered’’ by an enterprising inventor. Chak-rabarty, 447 U.S. at 309, 100 S.Ct. 2204.

Even when an invention does not existin nature in the claimed state, it may stillbe directed to subject matter that is notpatentable. For example, in Funk Broth-ers, the Supreme Court held a patent to acombination of multiple naturally occur-ring bacterial strains was not patentable.Although there was ‘‘an advantage in thecombination,’’ which was apparently ‘‘newand useful,’’ none of the bacterial strains‘‘acquire[d] a different use’’ in combination.Funk Bros., 333 U.S. at 131–32, 68 S.Ct.440. The aggregation of the bacterialstrains into a single product produced ‘‘nonew bacteria, no change in the six speciesof bacteria, and no enlargement of therange of their utility. Each species hasthe same effect it always had. The bacte-ria perform in their natural wayTTTT Theyserve the ends nature originally providedand act quite independently of any effortof the patentee.’’ Id.

In contrast, the Supreme Court heldbacteria that included extra genetic mate-rial introduced by the inventor were ‘‘anonnaturally occurring manufacture orcomposition of matter—a product of hu-man ingenuity ‘having a distinctive name,character [and] use’ ’’ and therefore pat-entable. Chakrabarty, 447 U.S. at 309–310, 100 S.Ct. 2204 (quoting Hartranft v.Wiegmann, 121 U.S. 609, 615, 7 S.Ct. 1240,30 L.Ed. 1012 (1887)). Chakrabarty ex-plained that there is no distinction betweeninventions based on living and inanimateobjects for the purpose of the patent stat-ute; instead, the ‘‘relevant distinction’’ forthe section 101 analysis is ‘‘between prod-ucts of nature TTT and human-made inven-

tions.’’ Id. at 312–13, 100 S.Ct. 2204.Even if the invention was based on nature,and resulted in a living organism, it mayfall within the scope of section 101. Forexample, ‘‘the work of the plant breeder ‘inaid of nature’ was patentable invention’’because ‘‘ ‘a plant discovery resulting fromcultivation is unique, isolated, and is notrepeated by nature, nor can it be repro-duced by nature unaided by man.’ ’’ Id.(quoting S.Rep. No. 315, 71st Cong., 2dSess., 6–8 (1930)). In Chakrabarty, theintervention of man resulted in bacteriawith ‘‘markedly different characteristics’’from nature and ‘‘the potential for signifi-cant utility,’’ resulting in patentable sub-ject matter. Id. at 310, 100 S.Ct. 2204.

Funk Brothers and Chakrabarty do notstake out the exact bounds of patentablesubject matter. Instead, each applies aflexible test to the specific question pre-sented in order to determine whether theclaimed invention falls within one of thejudicial exceptions to patentability. FunkBrothers indicates that an invention which‘‘serve[s] the ends nature originally provid-ed’’ is likely unpatentable subject matter,but an invention that is an ‘‘enlargement ofthe range of TTT utility’’ as compared tonature may be patentable. 333 U.S. at131, 68 S.Ct. 440. Likewise, Chakrabartyillustrates that an invention with a distinc-tive name, character, and use, e.g., mark-edly different characteristics with the po-tential for significant utility, is patentablesubject matter. 447 U.S. at 309–10, 100S.Ct. 2204. Although the two cases resultin different outcomes, the inquiry itself issimilar.

Courts applied an analogous patentabili-ty inquiry long before Funk Brothers orChakrabarty. In one notable case, JudgeLearned Hand held that purified adrena-line, a natural product, was patentablesubject matter. Judge Hand explainedthat even if the claimed purified adrenaline


were ‘‘merely an extracted product withoutchange, there is no rule that such productsare not patentable.’’ Parke–Davis & Co.v. H.K. Mulford Co., 189 F. 95, 103(S.D.N.Y.1911). This is because ‘‘while itis of course possible logically to call this apurification of the principle’’ the resultingpurified adrenaline was ‘‘for every prac-tical purpose a new thing commerciallyand therapeutically.’’ Id. Similarly, in acase applying the Patent Act of 1952,1

purified vitamin B–12, another naturalproduct, was also held patentable subjectmatter within the meaning of section 101.Merck & Co. v. Olin Mathieson Chem.Corp., 253 F.2d 156 (4th Cir.1958). TheFourth Circuit explained that purified vita-min B–12 was ‘‘far from the premise of the[naturally occurring] principleTTTT Thenew product, not just the method, hadsuch advantageous characteristics as to re-place the [naturally occurring] liver prod-ucts. What was produced was, in nosense, an old product.’’ Id. at 162–63.These purified pharmaceutical cases areboth consistent with Supreme Court prece-dent: the purified substance was ‘‘a newthing TTT therapeutically,’’ Parke–Davis,189 F. at 103, and had such ‘‘advantageouscharacteristics’’ that what was produced bypurification ‘‘was, in no sense, an old prod-uct.’’ Merck, 253 F.2d at 162–63. In oth-er words, the purified natural productswere held to have ‘‘markedly differentcharacteristics,’’ as compared to the im-pure products, which resulted in ‘‘the po-tential for significant utility.’’ Chakrabar-ty, 447 U.S. at 310, 100 S.Ct. 2204.

In contrast, mere purification of a natu-rally occurring element is typically insuffi-cient to make it patentable subject matter.For example, our predecessor court heldthat claims to purified vanadium and puri-

fied uranium were not patentable subjectmatter since these were naturally occur-ring elements with inherent physical prop-erties unchanged upon purification. SeeIn re Marden, 18 CCPA 1057, 47 F.2d 958,959 (1931) (‘‘[P]ure vanadium is not new inthe inventive sense, and, it being a productof nature, no one is entitled to a monopolyof the same.’’); In re Marden, 18 CCPA1046, 47 F.2d 957 (1931) (‘‘ductile uranium’’not patentable because uranium is inher-ently ductile). Likewise, claims to purifiedductile tungsten were not patentable sub-ject matter since pure tungsten existed innature and was inherently ductile. Gener-al Electric Co. v. De Forest Radio Co., 28F.2d 641, 643 (3d Cir.1928). In each ofthese cases, purification did not result inan element with new properties. Instead,the court held the naturally occurring ele-ment inherently had the same characteris-tics and utility (e.g. ductility) as theclaimed invention. Consistent with FunkBrothers and Chakrabarty, the claims allfell within the laws of nature exception.

As illustrated by these examples, courtshave long applied the principles articulatedin Funk Brothers and Chakrabarty to dif-ferent factual scenarios in order to deter-mine whether an invention, as claimed,falls into the laws of nature exception. Isee no reason to deviate from this long-standing flexible approach in this case.

II.

We reconsider whether the claims atissue in this case are directed to patenta-ble subject matter following the remandfrom the Supreme Court in light of itsopinion in Mayo Collaborative Services v.Prometheus Laboratories, Inc., ––– U.S.––––, 132 S.Ct. 1289, 182 L.Ed.2d 321(2012) (Prometheus ). While the Prome-

1. The Patent Act of 1952 was the first timepatentable subject matter (the current section101) was separated out from novelty (the cur-

rent section 102). Previously, these two con-cepts were combined into a single section.


theus decision does not control the out-come in this case, it is nonetheless instruc-tive regarding the scope of the law ofnature exception. As an initial matter, thePrometheus discussion of laws of nature(process claims) clearly ought to applyequally to manifestations of nature (com-position claims). Myriad’s argument thatPrometheus is constrained to methods isan untenable position.

As the Prometheus court explained: ‘‘Ifa law of nature is not patentable, thenneither is a process reciting a law of na-ture, unless that process has additionalfeatures that provide practical assurancethat the process is more than a draftingeffort designed to monopolize the law ofnature itself.’’ Id. at 1297. Prometheusdid not, however, overturn Funk Brothersor Chakrabarty; cases clearly more analo-gous to the one before us. Using theframework of Funk Brothers and Chakra-barty in conjunction with the direction ofPrometheus, the applicable principles are:(1) laws of nature/manifestations of natureare not patentable; (2) a composition ofmatter with ‘‘markedly different character-istics’’ from that found in nature with thepotential for significant utility is directedto patentable subject matter.

Does the isolation process change theDNA from an unpatentable manifestationof nature into a patentable composition ofmatter? Id. at 1299. Does the claimedisolated DNA have markedly differentcharacteristics with the potential for signif-icant utility, e.g., an ‘‘enlargement of therange of TTT utility’’ as compared to na-ture? Chakrabarty, 447 U.S. at 309–310,100 S.Ct. 2204; Funk Bros., 333 U.S. at131, 68 S.Ct. 440.

The isolated DNA claims of the patentsin suit fall into two categories. The firstcategory of claims is directed to isolatedsequences that are identical to naturallyoccurring gene sequences. These include

claims encompassing both the isolated fulllength gene sequence (e.g. claim 1 of 8282patent), which are thousands of nucleo-tides, and claims to shorter isolated DNAstrands, with as few as fifteen nucleotides,whose nucleotide sequence is found on thechromosome (e.g. claim 5 of 8282 patent).The second category of claims is directedto isolated DNA sequences that are differ-ent from the naturally occurring gene se-quences. These include claims to isolatedcDNA molecules (e.g. claim 2 of the 8282patent), which differ from the natural genesequence in that the introns are removed,and are the opposite (complementary) se-quence of the naturally occurring RNA.

The cDNA claims present the easiestanalysis. Although the plaintiffs (nowplaintiff) in the suit argue, and the districtcourt held, that cDNA falls within the‘‘laws of nature’’ exception to section 101patentability, the claimed cDNA sequencesdo not exist in nature. Moreover, sincecDNA has all of the introns removed, andonly contains the coding nucleotides, it canbe used to express a protein in a cell whichdoes not normally produce it. Of course,the claimed isolated cDNA is inspired bynature—after all naturally occurring RNAis the template upon which cDNA is con-structed. Because it is used as a template,however, cDNA has a complementary se-quence of nucleotides, and therefore has acompletely different nucleotide sequencethan the RNA. Moreover, DNA has a dif-ferent chemical structure than RNA, in-cluding a different base (T instead of U,respectively) and sugar units (deoxyriboseinstead of ribose, respectively). This re-sults in, among other things, greater sta-bility for the DNA sequence as comparedto the RNA sequence.

cDNA sequences thus have a distinctivecharacter and use, with markedly differentchemical characteristics from either thenaturally occurring RNA or any continu-


ous DNA sequence found on the chromo-some. The claimed isolated cDNA se-quences are the creation of man, madeusing biological tools and the naturally oc-curring mRNA as a template. cDNA istherefore not one of the ‘‘ ‘manifestationsof TTT nature, free to all men and reservedexclusively to none’ ’’ that falls outside ofthe patent system. Chakrabarty, 447 U.S.at 309, 100 S.Ct. 2204 (quoting Funk Bros.,333 U.S. at 130, 68 S.Ct. 440). I decline toextend the laws of nature exception toreach entirely manmade sequences of iso-lated cDNA, even if those sequences areinspired by a natural template. I there-fore join the majority opinion with respectto the claims to cDNA sequences.2

DNA sequences that have the same pat-tern of DNA bases as a natural gene, inwhole or in part, present a more difficultissue. Unlike the isolated cDNA mole-cules, whose sequence is not present innature, the isolated DNA claims includenucleotide sequences which are found inthe human body, albeit as part of a muchlarger molecule, the chromosome. To theextent the majority rests its conclusion onthe chemical differences between genomicand isolated DNA (breaking the covalentbonds), I cannot agree that this is suffi-cient to hold that the claims to humangenes are directed to patentable subjectmatter. I agree that isolated genes are adifferent molecule and are therefore notsquarely analogous to unpatentable miner-als, created by nature without the assis-tance of man. The claimed isolated DNAmolecules, which are truncations (with dif-ferent ends) of the naturally occurringDNA found as part of the chromosome innature, are not naturally produced withoutthe intervention of man.

I begin with the short isolated sequencessuch as those covered by claim 5 which isdirected to ‘‘an isolated DNA having atleast 15 nucleotides of the DNA of claim1.’’ This claim covers a sequence as shortas 15 nucleotides and arguably as long asthe entire gene. For this claim to bepatent eligible, all of the sequences rang-ing from the 15 nucleotide sequence to thefull gene must be patentable subject mat-ter. The shorter isolated DNA sequenceshave a variety of applications and uses inisolation that are new and distinct as com-pared to the sequence as it occurs in na-ture. For example, these sequences canbe used as primers in a diagnostic screen-ing process to detect gene mutations.These smaller isolated DNA sequences—including isolated radiolabeled sequencesmirroring those on the chromosome—canalso be used as the basis for probes. Nat-urally occurring DNA cannot do this. Un-like the isolated DNA, naturally occurringDNA simply does not have the requisitechemical and physical properties needed toperform these functions.

The ability to use isolated DNA mole-cules as the basis for diagnostic genetictesting is clearly an ‘‘enlargement of therange of TTT utility’’ as compared to na-ture. Funk Bros., 333 U.S. at 131, 68S.Ct. 440. In Prometheus, the SupremeCourt held that the claims at issue werenot directed to patentable subject matterbecause they merely ‘‘set forth laws ofnature—namely, relationships betweenconcentrations of certain metabolites in theblood and the likelihood that a dosage of athiopurine drug will prove ineffective orcause harm.’’ 132 S.Ct. at 1296–97. Theclaimed relationship was ‘‘a consequence of

2. To the extent the claims to shorter portionsof cDNA include only naturally occurring se-quences found in the chromosome, for exam-

ple claim 6 of the 8282 patent, my reasoningis the same as for the isolated sequences ofclaim 5, discussed below.


the ways in which thiopurine compoundsare metabolized by the body—entirely nat-ural processes.’’ Id. at 1297.

There is no suggestion that the humanbody naturally uses 15–mers as primers tosynthesize DNA, or that the attendantprocess of ‘‘probing’’ a patient’s DNA todetect a mutation is somehow a naturallaw. The ability to use a short strand ofDNA as a primer or probe to determinewhether a patient has a mutation is a newand important utility substantially differ-ent from the role of that DNA as it occursin nature. Indeed, many of the plaintiffsin this case submitted declarations indicat-ing that they wanted to either offer suchtesting or receive such testing. UnlikePrometheus, the claims to short isolatedstrands of DNA are not directed to therelationship between the mutation andcancer, but rather to a new tool that canbe used to determine if that relationshipexists. The short isolated DNA sequenceshave markedly different properties whichare directly responsible for their new andsignificant utility. Chakrabarty, 447 U.S. at309–10, 100 S.Ct. 2204. It is not the chem-ical change alone, but that change com-bined with the different and beneficial util-ity that leads me to conclude that smallisolated DNA fragments are patentablesubject matter. Id. at 310, 100 S.Ct. 2204.

In fact, much of the dissent’s analysiswith regard to the full gene would seem to

support my conclusion that small isolatedDNA molecules are directed to patent-eligible subject matter. The dissent ex-plains why the baseball bat is directed topatent eligible subject matter: ‘‘man hasdefined the parts that are to be retainedand the parts that are to be discarded, andhe has molded the retained portion into aproduct that bears little resemblance tothat which occurs naturally.’’ Dissent at1353. The exact same thing is true withregard to primer and probe claims. Manhas whittled the chromosomal DNA mole-cule down to a 15 nucleotide sequence—defining the parts to be retained and dis-carded.3 And the result is a product witha function (primer or probe) that is entire-ly different from the full gene from whichit was obtained.4 I conclude that thesmall, isolated DNA molecules are an al-teration of the natural product ‘‘with mark-edly different characteristics from anyfound in nature and one having the poten-tial for significant utility.’’ 447 U.S. at310, 100 S.Ct. 2204.

Turning now to the longer strands ofisolated DNA, isolated strands which in-clude most or all of the gene present amore difficult case. Some of the claims atissue, for example 8282 patent claim 5, aregenus claims, drafted broadly enough toinclude both short fragments as well as theentire isolated gene sequence. While Iultimately conclude that these longer iso-lated sequences, including the isolated

3. If adding functionality to a naturally occur-ring molecule, for example adding a lipidchain, is a creation of man then removingfunctionality, for example truncating a natu-ral DNA sequence or protein to yield smallermolecules with new properties should also be.In either case, it is the intervention of manthat created a new molecule. After all, thehand of man is just as apparent in the David,created by removing stone from a block ofmarble, as the ceiling of the Sistine Chapel,

created by adding layers of paint to an exist-ing structure.

4. The dissent analogizes the full BRCA geneto a slab of marble found in the earth asdistinct from the sculpture carved into it—which the dissent indicates would be worthyof intellectual property protection. If themulti-thousand nucleotide BRCA gene is theslab, isn’t the 15 nucleotide primer the sculp-ture?


gene sequence as a whole, are also patent-able subject matter, I do so for a reasondifferent than for the shorter sequences.

All of the same structural argumentsapply to any length of isolated DNA so,like the shorter strands, an isolated DNAcoding for a gene does have a literal chem-ical difference from the gene as it appearson the chromosome. Unlike the shorterstrands of isolated DNA, the chemical andstructural differences in the isolated genedo not clearly lead to an ‘‘enlargement ofthe range of TTT utility’’ as compared tonature. Funk Bros., 333 U.S. at 131, 68S.Ct. 440. For example, the full lengthgene is too large to be used as a probe.See J.A. 4322 (a probe is a DNA moleculeusually 100–1,000 bases long). Likewise,an entire isolated gene appears unsuitablefor use as a primer in genetic screening formutations in that same gene. See J.A.4323 (Primers ‘‘are complementary to anexact location of a much larger targetDNA molecule.’’). The isolated full lengthgene does not clearly have a new utilityand appears to simply serve the same endsdevised by nature, namely to act as a geneencoding a protein sequence.

If I were deciding this case on a blankcanvas, I might conclude that an isolatedDNA sequence that includes most or all of

a gene is not patentable subject matter.The scope of the law of nature/manifesta-tion of nature exception was certainly en-larged in Prometheus. But we do notdecide this case on a blank canvas. Con-gress has, for centuries, authorized an ex-pansive scope of patentable subject matter.Likewise, the United States Patent Officehas allowed patents on isolated DNA se-quences for decades, and, more generally,has allowed patents on purified naturalproducts for centuries. There are nowthousands of patents with claims to isolat-ed DNA, and some unknown (but certainlylarge) number of patents to purified natu-ral products or fragments thereof.5 As Iexplain below, I believe we must be partic-ularly wary of expanding the judicial ex-ception to patentable subject matter whereboth settled expectations and extensiveproperty rights are involved.6

III.

For more than a decade the Patent Of-fice’s policy has been that ‘‘[a]n isolatedand purified DNA molecule that has thesame sequence as a naturally occurringgene is eligible for a patent because TTT

that DNA molecule does not occur in thatisolated form in natureTTTT’’ 66 Fed.Reg.1092, 1093 (Jan. 5, 2001). I do not agree

5. See, e.g., U.S. Patent 3,067,099 (claimingvancomycin, an antibiotic produced by bacte-ria found in soil) and U.S. Patent 4,552,701(claiming a vancomycin fragment producedby removing a sugar unit). A natural productfragment, for example a naturally occurringantibiotic with a sugar moiety removed, ishighly analogous to isolated DNA. In eachcase, the claimed molecule is a smaller frag-ment of a naturally occurring molecule, withsome naturally occurring functionality re-moved. See U.S. Patent 4,552,701, col.3–4(compare entry 2 with entries 10 and 13).

6. My analysis of the claims at issue assumesthat they do not include an isolated, full

length chromosome. I do not believe that aclaim to an entire chromosome, for examplechromosome 17, is patentable subject matter.First, there is no indication that the chromo-some in isolation has markedly different char-acteristics compared to the chromosome innature. Second, unlike claims to isolatedgenes, there is no indication of either settledexpectations or extensive property rights forclaims to isolated chromosomes. This is un-doubtedly due to the small number of chro-mosomes as compared to the number ofgenes.


with the dissent’s characterization of thePTO position as perfunctory. The PTOconcluded that isolated DNA is patentablebecause it is different from what is foundin nature—the process of synthesizing it orisolating it changes it. While the PTOlacks substantive rule making authority, itis not without expertise in this area. Theexplicit statement of the Patent Office’sposition on isolated DNA, however, is sim-ply a continuation of a longstanding andconsistent policy of allowing patents forisolated natural products. See id. (notingU.S. Patent 141,072, claiming ‘‘[y]east, freefrom organic germs of disease,’’ issued toLouis Pasteur in 1873); cf. In re Berg-strom, 57 CCPA 1240, 427 F.2d 1394(1970) (isolated prostaglandins patentable).According to the Patent Office, isolatedDNA is no different from the isolated nat-ural products of Parke–Davis. See 66Fed.Reg. at 1093 (quoting Parke–Davis ).

Even before the current guidelines for-malized the Patent Office’s position, itgranted patents to human genes in theearly 1980s, and subsequently issued thou-sands of patents on ‘‘isolated DNA.’’ Ma-jority at 1332–33. In fact, claims similarto the ones at issue in this case have beenthe focal point of important litigation. Forexample, Amgen, Inc. v. Chugai Pharma-ceutical Co., 927 F.2d 1200 (Fed.Cir.1991)involved a claim to ‘‘ ‘[a] purified and iso-lated DNA sequence consisting essentiallyof a DNA sequence encoding human eryth-ropoietin.’ ’’ Id. at 1203–04 (quoting U.S.Patent No. 4,703,008, claim 2). We af-firmed that this claim was valid and in-fringed. Id. at 1219. Erythropoietin, alsoknown as EPO, went on to become thebiggest-selling biotechnology drug devel-oped to that point, resulted in billions ofdollars in sales, and accounted for over50% of Amgen’s revenue in 1997. Amgen,Inc. v. Hoechst Marion Roussel, Inc., 126

F.Supp.2d 69, 77 (D.Mass.2001). IsolatedDNA claims, at least in the case of Amgen,represent crucial and exceedingly valuableproperty rights.

The settled expectations of the biotech-nology industry—not to mention the thou-sands of issued patents—cannot be takenlightly and deserve deference. This out-pouring of scientific creativity, spurred bythe patent system, reflects a substantialinvestment of time and money by the bio-technology industry to obtain propertyrights related to DNA sequences. Thetype of fundamental alteration in the scopeof patentable subject matter argued in thiscase ‘‘risk[s] destroying the legitimate ex-pectations of inventors in their property.’’Festo Corp. v. Shoketsu Kinzoku KogyoKabushiki Co., 535 U.S. 722, 739, 122 S.Ct.1831, 152 L.Ed.2d 944 (2002). I believeleaving intact the settled expectations ofproperty owners is particularly importantin light of the large number of propertyrights involved, both to isolated DNA andto purified natural products generally.

The Supreme Court has warned that‘‘courts must be cautious before adoptingchanges that disrupt the settled expecta-tions of the inventing community.’’ Id. at739, 122 S.Ct. 1831. The settled expecta-tions of the inventing community with re-spect to isolated DNA claims are builtupon the broad language of the statute,judicial precedent, such as Parke–Davisand Merck, and the Patent Office’s long-standing policy and practice. NeitherFunk Brothers nor Chakrabarty purportedto overrule either the early cases or thePatent Office’s practice; indeed, as dis-cussed supra, these cases weigh the sameconsiderations as Parke–Davis and Merck.‘‘ ‘To change so substantially the rules ofthe game now,’ ’’ after more than a centuryof practice, ‘‘ ‘could very well subvert the


various balances the PTO sought to strikewhen issuing the numerous patents whichhave not yet expired and which would beaffected by our decision.’ ’’ Festo, 535 U.S.at 739, 122 S.Ct. 1831 (quoting Warner–Jenkinson Co. v. Hilton Davis Chem. Co.,520 U.S. 17, 32 n. 6, 117 S.Ct. 1040, 137L.Ed.2d 146 (1997)).

Although the Patent Office has consis-tently followed the same policy for a dec-ade (and arguably a century or more), theUnited States, as an amicus, now arguesthat the Patent Office’s published guide-lines are incorrect and a misstatement ofthe law. In place of these guidelines, thegovernment suggested that a ‘‘magic mi-croscope’’ would provide a useful metaphorfor guiding our section 101 analysis. Themagic microscope, however, would not seethe claimed DNA molecules at issue in thiscase. An isolated DNA molecule has dif-ferent chemical bonds as compared to the‘‘unisolated’’ sequence in the chromosome(the ends are different). In short, theclaimed molecules cannot be seen in naturethrough the magic microscope. While youmay be able to see the order of DNAnucleotides in the chromosome, the isolat-ed fragment of DNA is a different mole-cule. Creating the claimed isolated DNAsequences therefore results in a distinctlyunnatural molecule.7 Even the dissentagrees that the isolated DNA molecules atissue require cleaving chemical bonds,though it disputes the importance of theresulting distinct ‘‘ ‘molecular species.’ ’’Dissent at 1350–51 (quoting Linus Pauling,

The Nature of the Chemical Bond 6 (3ded.1960)).

The dissent claims that the Patent Of-fice’s past views are ‘‘substantially under-mined by the position the government hastaken in this case.’’ Dissent at 1357–58.The Patent Office’s prior practice, howev-er, is particularly important since it result-ed in a large number of property rightsover the past decades. If the governmentdecided to change course in the PatentOffice, and decline to issue new patents toisolated genes, it would not impact theseexisting property rights. This, however, isnot what the government argues in thiscase. Instead the government argues foran entirely different interpretation of thelaw that would destroy existing propertyrights. Although the dissent points outthat Chakrabarty overturned the PatentOffice’s practice of denying patents to mi-croorganisms, there is a clear differencebetween allowing additional patent protec-tion where none previously existed, anddenying patent protection decades (or cen-turies) after the fact, thereby eliminating alarge number of property rights. Chakra-barty, consistent with the broad languageof the statute, allowed additional patentswhere none previously existed. In con-trast, the government proposes to destroyexisting property rights based on a judgemade exception to that same broad lan-guage. This is a dramatic step that Ibelieve is best left to the Congress.

Nevertheless, the government claimsthat ‘‘this is a pure question of law’’ and

7. This also illustrates why the government’sanalogies to situations dealing with elements,for example lithium, are inapposite. Evenassuming the government’s contention thatlithium does not currently exist in isolatedform in nature, it is nevertheless clear thatelemental lithium, a basic building block pro-vided by nature, at some point must havereacted with, e.g., water to form the naturally

occurring lithium salts. In contrast, an iso-lated DNA sequence did not necessarily existbefore reacting further to produce the corre-sponding naturally occurring chromosomalDNA. Unlike a lithium salt, the chromosomedoes not imply that an isolated DNA moleculeof 15 nucleotides—or even a gene—necessari-ly previously existed as an isolated moleculein nature.


that we can therefore feel free to ignorethe years of Patent Office practice and theaccompanying expectations that practicecreated within the industry. The govern-ment argues that we should not defer tothe broad language (all but unchangedsince 1793) provided by Congress in thepatent statute, or allow Congress to decidewhether it is necessary to correct the Pat-ent Office’s practice through legislation.It is tempting to use our judicial power inthis fashion, especially when the patents inquestion raise substantial moral and ethi-cal issues related to awarding a propertyright to isolated portions of human DNA—the very thing that makes us humans, andnot chimpanzees.

The invitation is tempting, but I declinethe opportunity to act where Congresshas chosen not to. Congress at least im-plicitly approved of the Patent Office’spolicy of awarding patents on genes andDNA sequences. For example, Congressincluded, as part of the Patent Office’sappropriations, language affirming thePatent Office’s interpretation of section101 to prohibit patents on human organ-isms. Consolidated Appropriations Act,2004, Pub.L. No. 108–199, § 634, 118 Stat.3, 101. Although Congress was aware

‘‘that there are many institutions TTT thathave extensive patents on human genes,’’149 Cong. Rec. H7248, H7274, it explicitlydeclined to implement legislation to ‘‘af-fect any of those current existing pat-ents.’’ 149 Cong. Rec. E2417–01. To thecontrary, it made clear that the languagerelated to ‘‘human organisms’’ was not in-tended to change the Patent Office’s poli-cy with respect to claims to genes, stemcells, or other similar inventions.8 Farfrom oblivious to the patenting of genes,Congress introduced and declined to passseveral bills which would put a moratori-um on gene patents,9 authorize fundingfor the study of whether genes ought tobe patentable,10 and exempt from patentinfringement anyone who uses patentedgenes for non-commercial research pur-poses or medical practitioners who usegenetic diagnostic tests.11 Congress isobviously aware of the issues presented inthis case and I believe ‘‘[a]ny recalibrationof the standard of [patentability] remainsin its hands.’’ Microsoft Corp. v. i4i Ltd.,––– U.S. ––––, 131 S.Ct. 2238, 2252, 180L.Ed.2d 131 (2011).

The judiciary cannot engage in an adhoc innovation-based analysis, which iswhy the exceptions to patentability apply

8. ‘‘What I want to point out is that the U.S.Patent Office has already issued patents ongenes, stem cells, animals with human genes,and a host of non-biologic products used byhumans, but it has not issued patents onclaims directed to human organisms, includ-ing human embryos and fetuses. My amend-ment would not affect the former, but wouldsimply affirm the latter.’’ 149 Cong. Rec.E2417–01 (emphasis added); see also 157Cong. Rec. E1177–04 (resubmitting this testi-mony in the context of the current patentreform legislation).

9. At least one bill was introduced in Congressto put a moratorium on patents to humangenes or gene sequences. See, e.g., The Ani-

mal and Gene Patent Moratorium Bill (S.3871993).

10. The Genomic Science and Technology In-novation Act of 2002 (H.R.3966).

11. The Genomic Research and Diagnostic Ac-cessibility Act of 2002 (H.R.3967). As thebill’s sponsor explained: ‘‘It is important tonote that this section would not overturn thecommercial rights of patent holders. If aresearch [organization] utilizing the exemp-tion makes a commercially viable finding, heor she would still have to negotiate any rightsto market the new discovery with the patentholder.’’ 148 Cong. Rec. E353–03.


only to the clearest cases: a new mineraldiscovered in the earth, or a new plantfound in the wild, or E=mc 2, or the law ofgravity. It is Congress, with ‘‘the consti-tutional authority and the institutionalability to accommodate fully the variedpermutations of competing interests thatare inevitably implicated by such new tech-nology,’’ Sony Corp. of America v. Univer-sal City Studios, Inc., 464 U.S. 417, 431,104 S.Ct. 774, 78 L.Ed.2d 574 (1984), whomust decide whether it is necessary tochange the scope of section 101 to excludethe kind of isolated DNA claims at issuehere. It is not clear to me that Chakra-barty, Funk Brothers, or Prometheusleads inexorably to the conclusion that iso-lated DNA molecules are not patentablesubject matter. I decline the invitation tobroaden the law of nature exception.

Given the complicated technology andconflicting incentives at issue here, anychange must come from Congress. SeeGottschalk v. Benson, 409 U.S. 63, 72–73,93 S.Ct. 253, 34 L.Ed.2d 273 (1972) (Asection 101 analysis raises ‘‘considerableproblems TTT which only committees ofCongress can manage, for broad powers ofinvestigation are needed, including hear-ings which canvass the wide variety ofviews which those operating in this fieldentertain. The technological problemstendered [by the parties] TTT indicate to usthat considered action by the Congress isneeded.’’).

IV.

‘‘The rule that the discovery of a law ofnature cannot be patented rests TTT on theTTT fundamental understanding that theyare not the kind of ‘discoveries’ that thestatute was enacted to protect.’’ Flook,437 U.S. at 593, 98 S.Ct. 2522. Is anisolated kidney patentable? Probably not,

but as far as I can tell nobody everthought isolating organs from someone’sbody was the kind of discovery ‘‘that thestatute was enacted to protect.’’ In con-trast, purifying or isolating natural prod-ucts has historically been exactly the kindof discovery protected by the patent stat-utes. There is a century-long history ofaffirming patent protection for isolatedand purified biological products rangingfrom hormones to vitamins to proteins toantibiotics. These inventions must haveseemed miraculous at the time, providingpreviously unknown therapeutic options totreat sickness. The fact that these mole-cules might have existed in nature did notforeclose patent protection in view of theextraordinary benefits accessible to manafter isolation.

The Patent Office has, for more than adecade, affirmatively stated its belief thatisolated DNA is patentable for the samereasons as isolated vitamins or hormones.There is no indication from Congress thatthis view is wrong; to the contrary, itappears Congress also believes DNA ispatentable. This long-term policy of pro-tecting isolated DNA molecules has result-ed in an explosion of innovation in thebiotechnology industry, an industry which,unlike the financial services industry oreven the software industry, depends onpatents to survive. Holding isolated DNAnot patentable would destroy long settledindustry expectations for no reason otherthan a gut feeling that DNA is too close tonature to be patentable, an arbitrary deci-sion based on a judge-made exception. Ibelieve that isolated DNA fragments,which have both chemical changes fromthe naturally occurring genomic DNA aswell as new utility, are ‘‘the kind of ‘discov-eries’ that the statute was enacted to pro-tect.’’ I therefore decline to extend the‘‘laws of nature’’ exception to include iso-lated DNA sequences.


This case typifies an observation by thelate Chief Judge Markey, our first ChiefJudge, that ‘‘[o]nly God works from noth-ing. Men must work with old elements.’’Fromson v. Advance Offset Plate, Inc., 755F.2d 1549, 1556 n. 3 (Fed.Cir.1985) (quota-tion, citations omitted). Human DNA is,for better or worse, one of the old ele-ments bequeathed to men to use in theirwork. The patents in this case revealed anew molecular understanding about our-selves; ‘‘the inventions most benefitingmankind are those that ‘push back thefrontiers of chemistry, physics, and thelike.’ ’’ Chakrabarty, 447 U.S. at 316, 100S.Ct. 2204 (quoting Great A. & P. Tea Co.v. Supermarket Corp., 340 U.S. 147, 154,71 S.Ct. 127, 95 L.Ed. 162 (1950)). Wecannot, after decades of patents and judi-cial precedent, now call human DNA fruitfrom the poisonous tree, and punish thoseinquisitive enough to investigate, isolate,and patent it. ‘‘Our task TTT is the narrowone of determining what Congress meantby the words it used in the statute; oncethat is done our powers are exhausted.’’Id. at 318, 100 S.Ct. 2204. This inquirydoes not have moral, ethical, or theologicalcomponents. Cf. id. at 316–17, 100 S.Ct.2204 (‘‘[W]e are without competence toentertain’’ arguments about ‘‘the graverisks’’ generated by genetic research.).‘‘The choice we are urged to make is amatter of high policy for resolution withinthe legislative process after the kind ofinvestigation, examination, and study thatlegislative bodies can provide and courtscannot.’’ Id. at 317, 100 S.Ct. 2204. Thepatents in this case might well deserve tobe excluded from the patent system, butthat is a debate for Congress to resolve. Iwill not strip an entire industry of theproperty rights it has invested in, earned,and owned for decades unchallenged underthe facts of this case.

BRYSON, Circuit Judge, concurring inpart and dissenting in part:

I concur with the portions of this court’sjudgment that are directed to standing,the patentability of the cDNA claims, andthe patentability of the method claims. Irespectfully dissent from the court’s hold-ing that Myriad’s BRCA gene claims andits claims to gene fragments are patent-eligible. In my view, those claims are notdirected to patentable subject matter, andthe court’s decision, if sustained, will likelyhave broad consequences, such aspreempting methods for whole-genome se-quencing, even though Myriad’s contribu-tion to the field is not remotely consonantwith such effects.

In its simplest form, the question in thiscase is whether an individual can obtainpatent rights to a human gene. From acommon-sense point of view, most observ-ers would answer, ‘‘Of course not. Patentsare for inventions. A human gene is notan invention.’’ The essence of Myriad’sargument in this case is to say that it hasnot patented a human gene, but somethingquite different—an isolated human gene,which differs from a native gene becausethe process of extracting it results inchanges in its molecular structure (al-though not in its genetic code). We aretherefore required to decide whether theprocess of isolating genetic material from ahuman DNA molecule makes the isolatedgenetic material a patentable invention.The court concludes that it does; I con-clude that it does not.

At the outset, it is important to identifythe inventive contribution underlying Myr-iad’s patents. Myriad was not the first tomap a BRCA gene to its chromosomallocation. That discovery was made by ateam of researchers led by Dr. Mary–Claire King. See Jeff M. Hall et al., Link-


age of Early–Onset Familial Breast Can-cer to Chromosome 17q21, 250 Science1684 (1990). And Myriad did not invent anew method of nucleotide sequencing. In-stead, it applied known sequencing tech-niques to identify the nucleotide order ofthe BRCA genes.1 Myriad’s discovery ofthose sequences entailed difficult work,and the identified sequences have had im-portant applications in the fight againstbreast cancer. But the discovery of thesequences is an unprotectable fact, justlike Dr. King’s discovery of the chromo-somal location of the BRCA1 gene.

Of course, Myriad is free to patent appli-cations of its discovery. As the first partywith knowledge of the sequences, Myriadwas in an excellent position to claim appli-cations of that knowledge. Many of itsunchallenged claims are limited to suchapplications. See, e.g., 8441 patent, claim21; 8492 patent, claim 22; 8282 patent,claim 9. Yet some of Myriad’s challengedcomposition claims effectively preempt anyattempt to sequence the BRCA genes, in-cluding whole-genome sequencing. In myview, those claims encompass unpatentablesubject matter, and a contrary ruling islikely to have substantial adverse effectson research and treatment in this impor-tant field.

I

As the majority and concurring opinionsexplain, the DNA claims at issue in thiscase fall into three categories: claims thatcover the isolated BRCA genes (claim 1 ofthe 8282 patent, claim 1 of the 8473 patent,and claims 1 and 6 of the 8492 patent);claims that cover only the BRCA cDNA

(claims 2 and 7 of the 8282 patent andclaim 7 of the 8492 patent); and claims thatcover portions of the BRCA genes andcDNA as small as 15 nucleotides long(claims 5 and 6 of the 8282 patent). I firstaddress the claims to the BRCA genes.

A

In the seminal case of Diamond v.Chakrabarty, 447 U.S. 303, 100 S.Ct. 2204,65 L.Ed.2d 144 (1980), the Supreme Courtheld that an artificial life form could bepatented. In the course of its opinion, andcritically for purposes of its reasoning, theCourt stated that not all living things orother items found in nature were subjectto patenting. The Court explained thatalthough the language of section 101 of thePatent Act is broad, it is not the case thatit ‘‘has no limits or that it embraces everydiscovery.’’ Id. at 309, 100 S.Ct. 2204.The Court then set forth the general prop-osition that ‘‘laws of nature, physical phe-nomena, and abstract ideas have been heldnot patentable.’’ Id. As examples, theCourt noted that ‘‘a new mineral discover-ed in the earth or a new plant found in thewild is not patentable subject matter.’’Thus, even though a mineral or a plant is a‘‘composition of matter,’’ and could beviewed as falling within a broad construc-tion of section 101, the Court explainedthat those ‘‘manifestations of TTT nature’’are not patentable subject matter, but are‘‘free to all men and reserved exclusivelyto none.’’ Id., quoting Funk Bros. SeedCo. v. Kalo Inoculant Co., 333 U.S. 127,130, 68 S.Ct. 440, 92 L.Ed. 588 (1948); seealso Bilski v. Kappos, ––– U.S. ––––, 130S.Ct. 3218, 3225, 177 L.Ed.2d 792 (2010).

1. There is some dispute over whether otherinventors helped Myriad discover the BRCAsequences or discovered the BRCA2 sequencebefore Myriad. Because those disputes are

irrelevant to the question of patentable sub-ject matter, I refer to the discovery of theBRCA sequences as Myriad’s work.


The Court in Chakrabarty held the arti-ficial life form at issue in that case to bepatentable because the claim was ‘‘not to ahitherto unknown natural phenomenon,but to a nonnaturally occurring manufac-ture or composition of matter—a productof human ingenuity ‘having a distinctivename, character [and] use.’ ’’ 447 U.S. at309–10, 100 S.Ct. 2204, quoting Hartranftv. Wiegmann, 121 U.S. 609, 615, 7 S.Ct.1240, 30 L.Ed. 1012 (1887). In distinguish-ing between naturally occurring sub-stances and nonnaturally occurring manu-factures, the Court relied heavily on itsearlier decision in Funk Brothers, in whichthe inventor discovered that certain usefulbacterial strains did not exert an inhibitiveeffect on one another. Based on that dis-covery, the inventor obtained a patent on amixed culture of those non-inhibitivestrains. The Supreme Court held theproduct unpatentable, however, becausethe bacteria remained structurally andfunctionally the same as in their naturalstate. Funk Bros., 333 U.S. at 131, 68S.Ct. 440. By contrast, because Chakra-barty had produced ‘‘a new bacterium withmarkedly different characteristics fromany found in nature and one having thepotential for significant utility,’’ the Courtheld Chakrabarty’s invention to be patent-able. Chakrabarty, 447 U.S. at 310, 100S.Ct. 2204.

B

Myriad’s claims to the isolated BRCAgenes seem to me to fall clearly on the‘‘unpatentable’’ side of the line the Courtdrew in Chakrabarty. Myriad is claimingthe genes themselves, which appear in na-ture on the chromosomes of living humanbeings. The only material change made to

those genes from their natural state is thechange that is necessarily incidental to theextraction of the genes from the environ-ment in which they are found in nature.While the process of extraction is no doubtdifficult, and may itself be patentable, theisolated genes are not materially differentfrom the native genes. In this respect, thegenes are analogous to the ‘‘new mineraldiscovered in the earth,’’ or the ‘‘new plantfound in the wild’’ that the Supreme Courtreferred to in Chakrabarty. It may bevery difficult to extract the newly foundmineral or to find, extract, and propagatethe newly discovered plant. But that doesnot make those naturally occurring itemsthe products of invention.

The same is true for human genes.Like some minerals, they are hard to ex-tract from their natural setting. Also likeminerals, they can be used for purposesthat would be infeasible if they remainedin their natural setting. And the processof extracting minerals, or taking cuttingsfrom wild plants, like the process of isolat-ing genetic material, can result in somephysical or chemical changes to the naturalsubstance. But such changes do not makeextracted minerals or plant cuttings pat-entable, and they should not have thateffect for isolated genes. In each case,merely isolating the products of nature byextracting them from their natural locationand making those alterations that are at-tendant to their extraction does not givethe extractor the right to patent the prod-ucts themselves.

The majority characterizes the isolatedgenes as new molecules and considersthem different substances from the corre-sponding native DNA.2 Because the nativeBRCA genes are chemically bonded to oth-

2. Although I recognize that Judge Lourie andJudge Moore, while reaching the same ulti-

mate conclusions, have taken analytical pathsthat differ in some respects, for convenience I


er genes and histone proteins, the majorityconcludes that cleaving those bonds to iso-late the BRCA genes turns the isolatedgenes into ‘‘different materials.’’ Yetthere is no magic to a chemical bond thatrequires us to recognize a new productwhen a chemical bond is created or bro-ken, but not when other atomic or molecu-lar forces are altered.3 A chemical bond ismerely a force between two atoms orgroups of atoms strong enough ‘‘to make itconvenient for the chemist to consider [theaggregate] as an independent molecularspecies.’’ Linus Pauling, The Nature ofthe Chemical Bond 6 (3d ed.1960). Weak-er interatomic forces will be broken when,for example, a dirty diamond is cleanedwith water or another solvent, but thatdoes not make the clean diamond a human-made invention. See Am. Fruit Growers,Inc. v. Brogdex Co., 283 U.S. 1, 12, 51 S.Ct.328, 75 L.Ed. 801 (1931) (cleaning a shellby acid and then grinding off a layer withan emery wheel did not convert it into adifferent product). Nor should it make adifference for purposes of patentability ifthe portion of a wild plant that is collectedfor purposes of later regeneration is sepa-rated from the original plant by chemicalmeans or by scissors.

If the changes in the DNA moleculethat occur as part of the process of iso-lation render the gene claims patentable,the same analysis would seem to apply tochemical elements that do not appear intheir atomic form in nature. For exam-

ple, isolated lithium does not occur natu-rally because it reacts with air and waterand thus is found in nature only as part ofa chemical compound, ionically bound toother elements. Robert E. Krebs, TheHistory and Use of Our Earth’s ChemicalElements 48 (2d ed.2006). Once isolated,lithium has many industrial applications,and in order to isolate lithium, it is neces-sary to break ionic bonds in the lithiumcompounds that are found in nature. Butit seems plain that elemental lithium (likeother elements) would not be patentablesubject matter, even if it could only beextracted from nature through an isolationprocess.

The principles underlying that analysisapply to genetic material as well. In orderto isolate the BRCA gene, it is necessaryto break chemical bonds that hold the genein its place in the body, but the geneticcoding sequence that is the subject of eachof the BRCA gene claims remains thesame whether the gene is in the body orisolated. If we are to apply the conven-tional nomenclature of any field to deter-mine whether Myriad’s isolated DNAclaims are ‘‘new,’’ it would seem to makemore sense to look to genetics, which pro-vides the language of the claims, than tochemistry. Aside from Myriad’s cDNAclaims, its composition claims are not de-fined by any particular chemical formula.For example, claim 1 of the 8282 patentcovers all isolated DNAs coding for theBRCA1 protein, with the protein being

will refer to Judge Lourie’s opinion as themajority opinion and Judge Moore’s opinionas the concurring opinion.

3. The majority characterizes the question inthis case as turning on the breaking of cova-lent bonds linking the BRCA genes to the restof the DNA in chromosomes 13 and 17, butits analysis appears to place patentableweight on the breaking of other chemicalbonds, such as the hydrogen bonds that are

broken when separating DNA from histonesor—in an example unrelated to this case—theionic bonds that are broken when lithium isderived from a salt. It is difficult to see whydifferences between types of chemical bondsshould matter for patentability purposes, andI see little support for such a distinction in thegoverning precedents.


defined by the amino acid sequence encod-ed by the naturally occurring BRCA1gene. From a molecular perspective, thatclaim covers a truly immense range ofsubstances from the cDNA that is 5,914nucleotides long to the isolated gene thatcontains more than 120,000 nucleotides.And the patent does not define the upperend of that range because the patent doesnot identify a unique nucleotide sequencefor the 120,000–nucleotide–long isolatedBRCA1 gene. Instead, the patent con-tains a sequence that is just 24,000 nucleo-tides long with numerous gaps denoted‘‘vvvvvvvvvvvv.’’ 8282 patent, fig. 10. Analmost incalculably large number of newmolecules could be created by filling inthose gaps with almost any nucleotide se-quence, and all of those molecules wouldfall within the scope of claim 1. Included inthat set are many important molecularvariations to the BRCA1 gene that Myriadhad not yet discovered and could not havechemically described. Yet those moleculeswould share only one unifying characteris-tic: each would code for the same proteinas the naturally occurring BRCA1 gene.

From a genetic perspective, that claimcovers one ‘‘composition of matter’’—theBRCA1 gene. The isolated BRCA genesare identical to the BRCA genes found onchromosomes 13 and 17. They have thesame sequence, they code for the sameproteins, and they represent the sameunits of heredity. It is true that theclaimed molecules have been cleaved andthat they possess terminal groups that dif-fer from those found on naturally occur-ring genes. The majority attaches signifi-cance to those facts. But the function ofthe isolated DNA molecules is attributablenot to the nature of the isolation processor to the identity of the terminal groups onthe molecules; the function of the claimedmolecules is dictated by the nucleotide se-

quence of the gene—a sequence that isdetermined by nature and that appears innature exactly as it appears in the claimedisolated DNA. During the transcriptionphase of protein synthesis, the BRCAgenes are separated from chromosomalproteins. The transcription process thenproceeds from a starting point called thepromoter to a stopping point often calledthe terminator. James D. Watson et al.,Molecular Biology of the Gene 382, 394–96(6th ed.2008). The only difference be-tween the naturally occurring BRCAgenes during transcription and the claimedisolated DNA is that the claimed geneshave been isolated according to nature’spredefined boundaries, i.e., at points thatpreserve the ability of the gene to expressthe protein for which it is coded.

In that respect, extracting a gene is akinto snapping a leaf from a tree. Like agene, a leaf has a natural starting andstopping point. It buds during springfrom the same place that it breaks off andfalls during autumn. Yet prematurelyplucking the leaf would not turn it into ahuman-made invention. See Intervet Inc.v. Merial Ltd., 617 F.3d 1282, 1295 (Fed.Cir.2010) (Dyk, J., concurring in part anddissenting in part). That would remaintrue if there were minor differences be-tween the plucked leaf and the fallen au-tumn leaf, unless those differences impart-ed ‘‘markedly different characteristics’’ tothe plucked leaf. Chakrabarty, 447 U.S.at 310, 100 S.Ct. 2204.

Another example underscores the prob-lem with characterizing the isolated geneas a patentable invention. A human kid-ney is a product of nature; it does notbecome a patentable invention when it isremoved from the body, even if the paten-tee has developed an improved procedurefor extracting the kidney, and even if the


improved procedure results in some physi-cal or chemical changes to the kidney atthe points where the kidney was attachedto the host body. But if that is so, thenwhy should an isolated gene be treateddifferently for purposes of section 101?While the isolation of a gene involves thealteration of a single molecule, it is difficultto accept that it should make a difference,for purposes of patentability, whether theisolated substance is part of a single mole-cule, as in the case of the BRCA genes, orpart of a very large aggregation of mole-cules, as in the case of a kidney.

Both the majority and the concurringopinions attach significant weight to thefact that the claimed coding portions of thenative BRCA genes are part of a muchlarger molecule and that the isolatedBRCA genes, being smaller molecules ex-tracted from the larger one, are thereforeman-made inventions. But to argue thatthe isolated BRCA gene is patentable be-cause in its native environment it is part ofa much larger structure is no more persua-sive than arguing that although an atommay not be patentable, a subatomic parti-cle is patentable because it was previouslypart of a larger structure, or that while atree is not patentable, a limb of the treebecomes a patentable invention when it isremoved from the tree.

Of course, it is an oversimplification tosay that something that can be character-ized as ‘‘isolated’’ or ‘‘extracted’’ from itsnatural setting always remains a naturalproduct and is not patentable. One couldsay, for example, that a baseball bat is‘‘extracted’’ or ‘‘isolated’’ from an ash tree,

but in that case the process of ‘‘extracting’’the baseball bat necessarily changes thenature, form, and use of the ash tree andthus results in a manmade manufacture,not a naturally occurring product. In thatsetting, man has defined the parts that areto be retained and the parts that are to bediscarded, and he has molded the retainedportion into a product that bears littleresemblance to that which occurs natural-ly. The result of the process of selection isa product with a function that is entirelydifferent from that of the raw materialfrom which it was obtained. In the case ofthe BRCA genes, by contrast, nature hasdefined the genes as independent entitiesby virtue of their capacity for protein syn-thesis and, ultimately, trait inheritance.Biochemists extract the target genes alonglines defined by nature so as to preservethe structure and function that the genepossessed in its natural environment. Insuch a case, the extraction of a product ina manner that retains the character andfunction of the product as found in naturedoes not result in the creation of a humaninvention.4 That principle was capturedby the Supreme Court’s statement inChakrabarty that the invention in thatcase was not to ‘‘a hitherto unknown natu-ral phenomenon, but to a nonnaturally oc-curring manufacture or composition ofmatter ‘having a distinctive name, charac-ter [and] use.’ ’’ 447 U.S. at 309–10, 100S.Ct. 2204.

Cases involving the ‘‘purification’’ of anatural substance employ similar analysis.Our predecessor court recognized thatmerely purifying a naturally occurringsubstance does not render the substance

4. By analogy, extracting a slab of marblefrom the earth does not give rise to protecta-ble intellectual property rights, but ‘‘extract-ing’’ a piece of sculpture from that slab ofmarble does. In the case of the BRCA gene

claims, what Myriad has claimed is more akinto the slab of marble found in the earth thanto the sculpture carved from it after its extrac-tion.


patentable unless it results in a markedchange in functionality. In re Merz, 25CCPA 1314, 97 F.2d 599, 601 (1938) (hold-ing that there was no right to a patent ona purer version of ultramarine, but recog-nizing that if a claimed article is ‘‘of suchpurity that it differs not only in degree butin kind it may be patentable’’); see also Inre King, 27 CCPA 754, 107 F.2d 618, 620(1939) (same, for purified vitamin C); In reMarden, 18 CCPA 1057, 47 F.2d 958, 959(1931) (same, for purified vanadium); Gen.Elec. Co. v. DeForest Radio Co., 28 F.2d641, 643 (3d Cir.1928) (same, for purifiedtungsten). On the other hand, the purifiednatural substance is patentable if the ‘‘pu-rification’’ results in a product with suchdistinct characteristics that it becomes ‘‘forevery practical purpose a new thing com-mercially and therapeutically.’’ Parke–Davis & Co. v. H.K. Mulford Co., 189 F.95, 103 (C.C.S.D.N.Y.1911); see alsoMerck & Co. v. Olin Mathieson Chem.Corp., 253 F.2d 156, 161–64 (4th Cir.1958)(holding that a purified composition of vita-min B–12 was patentable because the puri-fication process resulted in a product thatwas therapeutically effective, whereas thenatural form was not).

In sum, the test employed by the Su-preme Court in Chakrabarty requires usto focus on two things: (1) the similarity instructure between what is claimed andwhat is found in nature and (2) the similar-ity in utility between what is claimed andwhat is found in nature. What is claimedin the BRCA genes is the genetic codingmaterial; that material is the same, struc-turally and functionally, in both the nativegene and the isolated form of the gene.

The structural differences between theclaimed ‘‘isolated’’ genes and the corre-sponding portion of the native genes areirrelevant to the claim limitations, to the

functioning of the genes, and to their utili-ty in their isolated form. The use to whichthe genetic material can be put, i.e., deter-mining its sequence in a clinical setting, isnot a new use; it is only a consequence ofpossession. In order to sequence an iso-lated gene, each gene must function in thesame manner in the laboratory as it doesin the human body. Indeed, that identityof function in the isolated gene is the keyto its value. The naturally occurring ge-netic material thus has not been altered ina way that would matter under the stan-dard set forth in Chakrabarty. For thatreason, the isolation of the naturally occur-ring genetic material does not make theclaims to the isolated BRCA genes patent-eligible.

The Supreme Court’s recent decision inMayo Collaborative Services v. Prome-theus Laboratories, Inc., ––– U.S. ––––,132 S.Ct. 1289, 1293, 182 L.Ed.2d 321(2012), does not decide this case, but theCourt’s analysis is nonetheless instructive.In Mayo, which involved method claims,the representative claim involved the stepsof administering a drug to a subject, deter-mining a metabolite concentration in thesubject’s blood, and inferring the need fora change in dosage based on that metabol-ite concentration. Id. at 1295. The Courtfound that the method was not directed topatent-eligible subject matter because itcontributed nothing ‘‘inventive’’ to the lawof nature that lay at the heart of theclaimed invention, i.e., ‘‘the relationshipsbetween the concentration in the blood ofcertain thiopurine metabolites and the like-lihood that the drug dosage will be ineffec-tive or induce harmful side-effects.’’ Id. at1294. The Court examined ‘‘whether theclaims do significantly more than simplydescribe these natural relations’’ andwhether the ‘‘claims add enough to theirstatements of the correlations to allow the


processes they described to qualify as pat-ent-eligible processes that apply naturallaws.’’ Id. at 1297 (emphasis in original).In concluding that the claims did not add‘‘enough’’ to the natural laws, the Courtwas particularly persuaded by the fact that‘‘the steps of the claimed processes TTT

involve well-understood, routine, conven-tional activity previously engaged in byresearchers in the field.’’ Id. at 1294.

Just as a patent involving a law of na-ture must have an ‘‘inventive concept’’ thatdoes ‘‘significantly more than simply de-scribe TTT natural relations,’’ Mayo, 132S.Ct. at 1294, 1297, a patent involving aproduct of nature should have an inventiveconcept that involves more than merelyincidental changes to the naturally occur-ring product. In cases such as this one, inwhich the applicant claims a composition ofmatter that is nearly identical to a productof nature, it is appropriate to ask whetherthe applicant has done ‘‘enough’’ to distin-guish his alleged invention from the simi-lar product of nature. Has the applicantmade an ‘‘inventive’’ contribution to theproduct of nature? Does the claimed com-position involve more than ‘‘well-under-stood, routine, conventional’’ elements?Here, the answer to those questions is no.

Neither isolation of the naturally occur-ring material nor the resulting breaking ofcovalent bonds makes the claimed mole-cules patentable. We have previously stat-ed that ‘‘isolation of interesting compoundsis a mainstay of the chemist’s art,’’ andthat ‘‘[i]f it is known how to perform suchan isolation doing so ‘is likely the productnot of innovation but of ordinary skill andcommon sense.’ ’’ Aventis PharmaDeutschland GmbH v. Lupin, Ltd., 499F.3d 1293, 1302 (Fed.Cir.2007), quotingKSR Int’l Co. v. Teleflex, Inc., 550 U.S.398, 421, 127 S.Ct. 1727, 167 L.Ed.2d 705

(2007). Similarly, the structural changesancillary to the isolation of the gene do notrender these claims patentable. Thecleaving of covalent bonds incident to iso-lation is itself not inventive, and the factthat the cleaved molecules have terminalgroups that differ from the naturally oc-curring nucleotide sequences does nothingto add any inventive character to theclaimed molecules. The functional portionof the composition—the nucleotide se-quence—remains identical to that of thenaturally occurring gene.

The majority suggests that I have ‘‘fo-cus[ed] not on the differences between iso-lated and native DNAs, but on one similar-ity: their informational content.’’ In lightof Mayo, that approach seems appropriate.The informational content of the nucleotidesequences is the critical aspect of thesemolecules; the terminal groups added tothe molecules when the covalent bonds arebroken—to which the majority and concur-ring opinions attribute such significance—are not even mentioned in the claims. Thenucleotide sequences of the claimed mole-cules are the same as the nucleotide se-quences found in naturally occurring hu-man genes. In my view, that structuralsimilarity dwarfs the significance of thestructural differences between isolatedDNA and naturally occurring DNA, espe-cially where the structural differences aremerely ancillary to the breaking of cova-lent bonds, a process that is itself notinventive.

II

As noted, in addition to the BRCA geneclaims discussed above, the claims at issuein this appeal include four claims to BRCAcDNA and two claims to portions of theBRCA genes and cDNA as small as 15nucleotides long.


I agree with the court that the claims toBRCA cDNA are eligible for patenting.The cDNA cannot be isolated from nature,but instead must be created in the labora-tory.5 The end product is a human-madeinvention with distinct structure becausethe introns that are found in the nativegene are removed from the cDNA seg-ment. Additionally, the cDNA has a utili-ty not present in the naturally occurringBRCA DNA and mRNA because cDNAcan be attached to a promoter and insertedinto a non-human cell to drive protein ex-pression.

However, I disagree with the court as tothe two claims to short segments of DNAhaving at least 15 nucleotides. Claim 6 ofthe 8282 patent covers any sequence of theBRCA1 cDNA that is at least 15 nucleo-tides long. That claim encompasses eachBRCA1 exon, even though each exon isnaturally defined by transcription. More-over, because small sequences of DNA arerepeated throughout the three billion nu-cleotides of the human genome, the claimcovers portions of the cDNA of more than4% of human genes. It also covers por-tions of the DNA of nearly all humangenes. Accordingly, efforts to sequencealmost any gene could infringe claim 6even though Myriad’s specification hascontributed nothing to human understand-ing of other genes. Myriad is not entitledto such broad protection. See Mayo, 132S.Ct. at 1301, 1303 (examining ‘‘how muchfuture innovation is foreclosed relative tothe contribution of the inventor’’ and warn-ing of the ‘‘danger’’ that overly broad pat-ent claims might ‘‘foreclose[ ] more futureinvention than the underlying discoverycould reasonably justify’’).

Myriad could easily have claimed morenarrowly to achieve the utility it attachesto segments of cDNA. It contends thatthose segments can be used as probes andprimers. DNA probes must be chemicallyaltered or ‘‘tagged’’ before they can be soused, and Myriad could have claimed thetagged segments to achieve probe func-tionality. A claim to tagged segmentswould not encompass the BRCA1 exons.As to primer functionality, many of thecDNA segments will not work. Some willbe too long. Some will be too short.Some will be palindromic and fold in onthemselves. Myriad could have identifieda subset of the segments that work asprimers, and such a claim could be patent-able if it were limited to species with‘‘markedly different characteristics fromany found in nature and TTT having thepotential for significant utility.’’ Chakra-barty, 447 U.S. at 310, 100 S.Ct. 2204.The problem with claim 6 is that it is sobroad that it includes products of nature(the BRCA1 exons) and portions of othergenes; its validity is not salvaged becauseit includes some species that are not natu-ral. Accordingly, I would hold claim 6unpatentable.

The other claim to a short segment ofDNA, claim 5 of the 8282 patent, is breath-takingly broad. That claim covers anysegment of the DNA defined by claim 1,provided that the segment is at least 15nucleotides long. Claim 1, in turn, coversany isolated DNA that codes for theBRCA1 polypeptide. Thus, claim 5 wouldcover not only the isolated BRCA1 gene ineach of its numerous molecular variations,but also any sub-sequence of those mole-cules, including portions that fall in the

5. The appellees argue that the BRCA1 cDNAcan be isolated from nature, and they refer toa BRCA1 pseudogene called BRCA1P1 that isfound in the human genome. However, the

appellees have failed to demonstrate that thepseudogene consists of the same sequence asthe BRCA1 cDNA.


undefined range of those molecules denot-ed ‘‘vvvvvvvvvvvvv.’’ Claim 5 would there-fore be unpatentable for the same reasonsas claim 1 and claim 6.

Of course, in light of its breadth, claim 5of the 8282 patent is likely to be invalid onother grounds, and thus a ruling as topatent eligibility with respect to that claimmay be superfluous. Nonetheless, it isimportant to consider the effects of suchbroad patent claims on the biotechnologyindustry. While Myriad has emphasizedthe biotechnology industry’s need of patentprotection to encourage and reward re-search in this difficult and important field,there is another side to the coin. Broadclaims to genetic material present a signifi-cant obstacle to the next generation ofinnovation in genetic medicine—multiplextests and whole-genome sequencing. Newtechnologies are being developed to se-quence many genes or even an entire hu-man genome rapidly, but firms developingthose technologies are encountering athicket of patents. Secretary’s AdvisoryComm. on Genetics, Health, and Society,Dep’t of Health & Human Servs., GenePatents and Licensing Practices andTheir Impact on Patient Access to GeneticTests 49–62 (2010). In order to sequencean entire genome, a firm would have tolicense thousands of patents from manydifferent licensors. See id. at 50–51.Even if many of those patents includeclaims that are invalid for anticipation orobviousness, the costs involved in deter-mining the scope of all of those patentscould be prohibitive. See id. at 51–52;Rebecca S. Eisenberg, Noncompliance,Nonenforcement, Nonproblem? Rethink-ing the Anticommons in Biomedical Re-search, 45 Hou. L.Rev. 1059, 1076–1080(2008) (concluding that existing studies‘‘have focused relatively little attention ondownstream product development’’ and

that interviews accompanying those stud-ies suggest that, though smaller than ini-tially feared, the costs associated with thepatent thicket are ‘‘quite real in the calcu-lations of product-developing firms’’).

My colleagues assign significant weightto the fact that since 2001 the PTO hashad guidelines in place that have allowedpatents on entire human genes. They con-clude that those guidelines, and the PTO’searlier practice, are entitled to deferencefrom this court as to the question whetherpatents to isolated human genes constitutepatent-eligible subject matter. I think thePTO’s practice and guidelines are not enti-tled to significant weight, for several rea-sons.

First, as we have recognized, the PTOlacks substantive rulemaking authority asto issues such as patentability. AnimalLegal Def. Fund v. Quigg, 932 F.2d 920,930 (Fed.Cir.1991). In areas of patentscope, we owe deference only commensu-rate with ‘‘the thoroughness of its consid-eration and the validity of its reasoning.’’Merck & Co. v. Kessler, 80 F.3d 1543, 1550(Fed.Cir.1996). The comments that thePTO issued at the time of its 2001 guide-lines in response to suggestions that isolat-ed human genes were not patentable are,frankly, perfunctory. See John M. Conley& Roberte Makowski, Back to the Future:Rethinking the Product of Nature Doc-trine as a Barrier to Biotechnology Pat-ents, 85 J. Pat. & Trademark Off. Soc’y301 (2003). Because those comments, atleast on their face, do not reflect thoroughconsideration and study of the issue, I donot regard them as worthy of much weightin the analysis of this complex question.

Second, whatever force the PTO’s viewson the issue of patent eligibility may havehad in the past has, at the very least, beensubstantially undermined by the position


the government has taken in this case.The Department of Justice has twice fileda brief on behalf of the United States inthis court taking the position that Myriad’sgene claims (other than the cDNA claims)are not patent-eligible. Although the PTOdid not ‘‘sign’’ the brief on either occasionand we are left to guess about the status ofany possible continuing inter-agency dis-agreements about the issue, the Depart-ment of Justice speaks for the ExecutiveBranch, and the PTO is part of the Execu-tive Branch, so it is fair to conclude thatthe Executive Branch has modified its po-sition from the one taken by the PTO in its2001 guidelines and, informally, beforethat.

Finally, prior to the Supreme Court’sdecision in Chakrabarty, the PTO had de-termined that microorganisms were notsubject to patenting, but the SupremeCourt gave no indication that it regardedthat view as entitled to deference. More-over, the Court gave short shrift to theCommissioner’s contention (which wasmade the lead argument in the govern-ment’s brief in that case) that the patenta-bility of life-forms was an issue that shouldbe left to Congress. Citing Marbury v.Madison, 5 U.S. (1 Cranch) 137, 2 L.Ed.60 (1803), the Court explained that ‘‘Con-gress has performed its constitutional rolein defining patentable subject matter in§ 101; we perform ours in construing thelanguage Congress has employed.’’ Chak-rabarty, 447 U.S. at 315, 100 S.Ct. 2204.We have the same responsibility andshould not shy away from deciding theissues of law that the parties have brought

to us. Although my colleagues believe ouranalysis of the legal question in this caseshould be influenced by purported expecta-tions of the inventing community based onthe PTO’s past practice of issuing patentson human genes, that is in effect to givethe PTO lawmaking authority that Con-gress has not accorded it.6 There is nocollective right of adverse possession tointellectual property, and we should notcreate one. Our role is to interpret thelaw that Congress has written in accor-dance with the governing precedents. Iwould do so and would affirm the districtcourt’s rulings as to the BRCA gene andBRCA gene segment claims.

,

AFTG–TG, LLC and Phillip M.Adams & Associates, LLC,

Plaintiffs–Appellants,

v.

NUVOTON TECHNOLOGY CORPO-RATION and Nuvoton TechnologyCorporation America, Defendants,

and

Pegatron Corporation, Pegatron Tech-nology Service, Inc., and Unihan,

Defendants–Appellees.

6. Because the asserted reliance interest isbased on PTO practice and not on prior judi-cial decisions, this case is not analogous toWarner–Jenkinson Co. v. Hilton Davis Chemi-cal Co., 520 U.S. 17, 117 S.Ct. 1040, 137L.Ed.2d 146 (1997), or Festo Corp. v. Shoketsu

Kinzoku Kogyo Kabushiki Co., 535 U.S. 722,122 S.Ct. 1831, 152 L.Ed.2d 944 (2002),where the expectations of the inventing com-munity were based on longstanding SupremeCourt precedent.

ASS’N FOR MOLECULAR PATHOLOGY v. U.S. P.T.O. …...ASS’N FOR MOLECULAR PATHOLOGY v. U.S....

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