ASS’N FOR MOLECULAR PATHOLOGY v. USPTO 181unclaw.com/chin/teaching/patent/Myriad -...

181ASS’N FOR MOLECULAR PATHOLOGY v. USPTOCite as 702 F.Supp.2d 181 (S.D.N.Y. 2010)

In re Assicurazioni, 228 F.Supp.2d at 373(internal citations and quotation marksomitted). It is clear to the Court, from itsown supervision of this case, that the fo-rum selection clause was not incorporatedinto the contract through fraud or over-reaching. There is also no indication thatthe clause contravenes public policy or thatthe law of Michigan would deprive Mercerof a remedy in this case. Moreover, al-though Mercer’s letter claims in the mostgeneral of terms that the Michigan forumis inconvenient, he does not explain howenforcing the forum selection clause wouldwork a gravely inconvenient or unfair re-sult. See Strategic Mktg. & Commc’n,Inc. v. Kmart Corp., 41 F.Supp.2d 268, 274(S.D.N.Y.1998) (observing that the ‘‘mereinconvenience and expense of traveling arenot themselves adequate reasons to dis-turb the parties’ contractual choice of fo-rum.’’). Ultimately, there is simply nosound reason why the contract’s forumselection clause should not be honored.

To summarize, the Court finds that: (1)Mercer signed the contract containing theforum selection provision; (2) the forumselection clause is enforceable; and (3) theforum selection clause is broad enough toencompass the parties’ dispute. Accord-ingly, Taylor’s Fed.R.Civ.P. 12(b)(1) mo-tion is granted.

III. CONCLUSION

Taylor’s Fed.R.Civ.P. 12(b)(1) motion isgranted. The Clerk of the Court is direct-ed to transfer this case to the appropriatetrial court in Houghton County, Michigan.

SO ORDERED.

,

ASSOCIATION FOR MOLECULARPATHOLOGY, et al.,

Plaintiffs,

v.

UNITED STATES PATENT ANDTRADEMARK OFFICE, et

al., Defendants.

No. 09 Civ. 4515.

United States District Court,S.D. New York.

March 29, 2010.

As Amended April 5, 2010.

Background: Competitor brought actionagainst patentee and Patent and Trade-mark Office (PTO), challenging validity ofpatents for isolated DNA containing breastcancer susceptibility genes and for meth-ods of analyzing gene sequences to identifymutations correlating with predispositionto breast cancer. Competitor and patenteecross-moved for summary judgment, andPTO moved for judgment on the pleadings.

Holdings: The District Court, Sweet, J.,held that:

(1) patents for isolated DNA containingbreast cancer susceptibility genes wereinvalid, and

(2) patents for methods of analyzing genesequences were invalid.

Ordered accordingly.

1. Patents O165(2), 314(5)

Before considering the patent-eligibili-ty of a claim, the disputed terms in theclaim must be construed in order to ensurethe claim’s scope is accurately assessed;courts are charged with interpreting dis-puted claim terms as a matter of law. 35U.S.C.A. § 101.

182 702 FEDERAL SUPPLEMENT, 2d SERIES

2. Patents O161, 167(1)In interpreting the meaning of patent

claim terms, words of a claim are generallygiven their ordinary and customary mean-ing to a person of ordinary skill in the artat the time of invention; the person ofordinary skill in the art is deemed to readthe claim terms not only in the context ofthe particular claim in which the disputedterm appears, but in the context of theentire patent, including the specification.

3. Patents O165(1)In interpreting patent claim terms,

the claims themselves provide substantialguidance as to the meaning of particularterms.

4. Patents O167(1)Patent claim language must be read in

the context of the specification.

5. Patents O162When a patentee acts as his or her

own lexicographer and includes an explicitdefinition of a claim term in the specifica-tion, that definition is dispositive over anyordinary meaning.

6. Patents O159In interpreting patent claim terms,

courts may rely on extrinsic evidence suchas dictionaries, treatises, and expert testi-mony, which may serve to provide a sourceof accepted meaning of terms used in vari-ous fields of science and technology orbackground on the technology at issue;however, such extrinsic evidence is lesssignificant than the intrinsic record in de-termining the legally operative meaning ofthe claim language.

7. Patents O101(2)Term ‘‘DNA,’’ in patents for isolated

DNA containing breast cancer susceptibili-ty genes and for methods of analyzinggene sequences to identify mutations cor-relating with predisposition to breast can-

cer, referred to physical manifestation ofthe acid that may be substantially separat-ed from other cellular components natural-ly accompanying a gene.

8. Patents O101(2)

Term ‘‘isolated DNA,’’ in patents forisolated DNA containing breast cancersusceptibility genes and for methods ofanalyzing gene sequences to identify muta-tions correlating with predisposition tobreast cancer, referred to segments ofDNA nucleotides existing separate fromother cellular components normally associ-ated with native DNA.

9. Patents O6Rule that the discovery of a law of

nature cannot be patented rests, not on thenotion that natural phenomena are notprocesses, but rather on the more funda-mental understanding that they are notthe kind of discovery that the patent stat-ute was enacted to protect. 35 U.S.C.A.§ 101.

10. Patents O5The inquiry into an invention’s patent

eligibility is a fundamental one, and assuch, the obligation to determine whattype of discovery is sought to be patentedmust precede the determination of wheth-er that discovery is, in fact, new or obvi-ous. 35 U.S.C.A. § 101.

11. Patents O6Isolated DNA containing breast can-

cer susceptibility genes was not patentablesubject matter; isolated DNA claimed bypatentee did not possess markedly differ-ent characteristics from native DNA foundin human cells, despite differences in theirstructural and functional capacities. 35U.S.C.A. § 101.

12. Patents O7.11Under the machine or transformation

test, a claimed process is patent-eligible if:


(1) it is tied to a particular machine orapparatus, or (2) it transforms a particulararticle into a different state or thing. 35U.S.C.A. § 101.

13. Patents O7.11

The use of a specific machine or thetransformation of an article must imposemeaningful limits on a claim’s scope toimpart patent-eligibility under the machineor transformation test, and the involve-ment of the machine or transformation inthe claimed process must not merely beinsignificant extra-solution activity. 35U.S.C.A. § 101.

14. Patents O7.14

Patentee’s methods of analyzing iso-lated DNA gene sequences to identify mu-tations correlating with predisposition tobreast cancer were not patentable subjectmatter under machine or transformationtest; patentee’s methods were directedonly to abstract mental processes of com-paring or analyzing gene sequences. 35U.S.C.A. § 101.

15. Patents O7.14

Patentee’s method of identifying po-tential cancer therapeutics by utilizingcells injected with altered breast cancersusceptibility genes was not patentablesubject matter under machine or transfor-mation test; patentee’s claimed processwas simply the scientific method. 35U.S.C.A. § 101.

16. Patents O2

Doctrine of constitutional avoidanceprecluded district court from addressingcompetitor’s claim that Patent and Trade-

mark Office (PTO) policy allowing forgrant of patents for isolated DNA contain-ing breast cancer susceptibility genes andfor methods of analyzing gene sequencesto identify mutations correlating with pre-disposition to breast cancer violated patentclause of Article I; patents were held inval-id, and decision by federal circuit court orSupreme Court affirming district court’sholding would be binding on PTO.U.S.C.A. Const. Art. 1, § 8, cl. 8.

Patents O328(2)

5,693,473, 5,709,999, 5,710,001, 5,747,-282, 5,753,441, 5,837,492, 6,033,857. Inval-id.

American Civil Liberties Union Founda-tion, by Christopher A. Hansen, Esq.,Aden Fine, Esq., Lenora M. Lapidus,Esq., Sandra S. Park, Esq., Public PatentFoundation, Benjamin N. Cardozo Schoolof Law, by Daniel B. Ravicher, Esq., NewYork, NY, for Plaintiffs.

Preet Bharara, United States Attorneyfor the Southern District of New York, byRoss Morrison, Esq., New York, NY, forDefendant USPTO.

Jones Day, by Brian M. Poissant, Esq.,Barry R. Satine, Esq., Laura A. Coruzzi,Esq., New York, NY, for Defendants Myr-iad Genetics and Directors of the Universi-ty of Utah Research Foundation.

OPINION

SWEET, District Judge.

TABLE OF CONTENTS

I. PRIOR PROCEEDINGSTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT186

II. THE PARTIES AND AMICI TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT186

III. THE FACTS TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT192


A. The Development of Genetics as a Field of Knowledge. TTTTTTTTTTTTTTTTTTTT192B. Molecular Biology and Gene Sequencing TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT193

1. DNATTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT1932. Extracted and purified DNA TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT1963. RNATTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT1974. cDNA TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT1985. DNA sequencing TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT199

C. The Development of the Patents-in-Suit TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT200D. Application of the Patents-in-SuitTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT203

1. Myriad’s BRCA1/2 testing TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT2032. Funding for Myriad’s BRCA1/2 tests TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT2033. Myriad’s enforcement of the patents-in-suit TTTTTTTTTTTTTTTTTTTTTTTTTT204

E. Disputed Issues TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT2061. The impact of Myriad’s patents on BRCA1/2 testing TTTTTTTTTTTTTTTTTTT2062. The impact of gene patents on the advancement of science and

medical treatment TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT207

IV. THE PATENTS TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT211A. Summary of the Patents TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT211B. Construction of the Claims TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT214

1. Legal standard TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT2142. Resolution of the disputed claim terms TTTTTTTTTTTTTTTTTTTTTTTTTTTTTT216

a. ‘‘DNA’’ and ‘‘isolated DNA’’ TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT216b. ‘‘BRCA1’’ and ‘‘BRCA2’’ TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT217

V. CONCLUSIONS OF LAW TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT217

A. The Summary Judgment Standard TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT217B. 35 U.S.C. § 101 and Its Scope TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT218C. The Composition Claims Are Invalid Under 35 U.S.C. § 101 TTTTTTTTTTTTTTT220

1. Consideration of the merits of Plaintiffs’ challenge is appropriateTTTTT2202. Patentable subject matter must be ‘‘markedly different’’ from a

product of nature TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT2223. The claimed isolated DNA is not ‘‘markedly different’’ from native

DNATTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT227D. The Method Claims are Invalid Under 35 U.S.C. § 101TTTTTTTTTTTTTTTTTTTT232

1. The claims for ‘‘analyzing’’ and ‘‘comparing’’ DNA sequences areinvalid under § 101 TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT233

2. The claim for ‘‘comparing’’ the growth rate of cells is invalid under§ 101 TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT237

E. The Constitutional Claims Against the USPTO Are Dismissed TTTTTTTTTTTTT237

VIII. CONCLUSION TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT238

Plaintiffs Association for Molecular Pa-thology, et al. (collectively ‘‘Plaintiffs’’)have moved for summary judgment pursu-ant to Rule 56, Fed.R.Civ.P., to declareinvalid fifteen claims (the ‘‘claims-in-suit’’)contained in seven patents (the ‘‘patents-in-suit’’) relating to the human BRCA1 andBRCA2 genes (Breast Cancer Susceptibili-ty Genes 1 and 2) (collectively, ‘‘BRCA1/2’’)under each of (1) the Patent Act, 35 U.S.C.§ 101 (1952), (2) Article I, Section 8,Clause 8 of the United States Constitution,

and (3) the First and Fourteenth Amend-ments of the Constitution because the pat-ent claims cover products of nature, lawsof nature and/or natural phenomena, andabstract ideas or basic human knowledgeor thought. The defendant United StatesPatent and Trademark Office (‘‘USPTO’’)issued the patents-in-suit which are heldby defendants Myriad Genetics and theUniversity of Utah Research Foundation(‘‘UURF’’) (collectively ‘‘Myriad’’ or the‘‘Myriad Defendants’’). Myriad has cross-


moved under Rule 56, Fed.R.Civ.P., forsummary judgment dismissing Plaintiffs’complaint, and the USPTO has cross-moved under Rule 12(c), Fed.R.Civ.P., forjudgment on the pleadings. Based uponthe findings and conclusions set forth be-low, the motion of Plaintiffs to declare theclaims-in-suit invalid is granted, the cross-motion of Myriad is denied, and the motionof the USPTO is granted.

As discussed infra in greater detail, thechallenged patent claims are directed to(1) isolated DNA containing all or portionsof the BRCA1 and BRCA2 gene sequenceand (2) methods for ‘‘comparing’’ or ‘‘ana-lyzing’’ BRCA1 and BRCA2 gene se-quences to identify the presence of muta-tions correlating with a predisposition tobreast or ovarian cancer. Plaintiffs’ chal-lenge to the validity of these claims, andthe arguments presented by the partiesand amici, have presented a unique andchallenging question:

Are isolated human genes and the com-parison of their sequences patentable?

Two complicated areas of science andlaw are involved: molecular biology andpatent law. The task is to seek the gov-erning principles in each and to determinethe essential elements of the claimed bio-logical compositions and processes andtheir relationship to the laws of nature.The resolution of the issues presented tothis Court deeply concerns breast cancerpatients, medical professionals, research-ers, caregivers, advocacy groups, existinggene patent holders and their investors,and those seeking to advance public health.

The claims-in-suit directed to ‘‘isolatedDNA’’ containing human BRCA1/2 genesequences reflect the USPTO’s practice ofgranting patents on DNA sequences so

long as those sequences are claimed in theform of ‘‘isolated DNA.’’ This practice ispremised on the view that DNA should betreated no differently from any otherchemical compound, and that its purifica-tion from the body, using well-known tech-niques, renders it patentable by transform-ing it into something distinctly different incharacter. Many, however, including sci-entists in the fields of molecular biologyand genomics, have considered this prac-tice a ‘‘lawyer’s trick’’ 1 that circumventsthe prohibitions on the direct patenting ofthe DNA in our bodies but which, in prac-tice, reaches the same result. The resolu-tion of these motions is based upon longrecognized principles of molecular biologyand genetics: DNA represents the physi-cal embodiment of biological information,distinct in its essential characteristics fromany other chemical found in nature. It isconcluded that DNA’s existence in an ‘‘iso-lated’’ form alters neither this fundamentalquality of DNA as it exists in the body northe information it encodes. Therefore, thepatents at issue directed to ‘‘isolatedDNA’’ containing sequences found in na-ture are unsustainable as a matter of lawand are deemed unpatentable subject mat-ter under 35 U.S.C. § 101.

Similarly, because the claimed compari-sons of DNA sequences are abstract men-tal processes, they also constitute unpat-entable subject matter under § 101.

The facts relating to molecular biologyare fundamental to the patents at issueand to the conclusions reached. Conse-quently, in the findings which follow, thediscussion of molecular biology precedesthe facts concerning the development, ap-plication, and description of the patents.Following those facts are the conclusionswhich compel the partial grant of summary

1. See, e.g., John M. Conley & Roberte Mar-kowski, Back to the Future: Rethinking theProduct of Nature Doctrine as a Barrier to

Biotechnology Patents, 85 J. Pat. & TrademarkOff. Soc’y 301, 305 (2003).


judgment to the Plaintiffs, the denial ofMyriad’s cross-motion, and the grant ofthe USPTO’s motion for judgment on thepleadings.

I. PRIOR PROCEEDINGS

The complaint in this action was filed onMay 12, 2009, alleging violations of 35U.S.C. § 101; Article I, Section 8, Clause8 of the United States Constitution; andthe First and Fourteenth Amendments tothe Constitution.

Defendants moved to dismiss the com-plaint which motion was denied by theopinion of November 1, 2009. See Assoc.for Molecular Pathology v. U.S. Patentand Trademark Office, 669 F.Supp.2d 365(S.D.N.Y.2009). Plaintiffs were found tohave the necessary standing to assert theirdeclaratory judgment claims against theMyriad Defendants and the USPTO, andspecific personal jurisdiction was found toexist over the Directors of the UURF byvirtue of acts performed in their officialcapacity that were directed to the state ofNew York. It was also determined thatthis Court possessed the necessary subjectmatter jurisdiction to hear Plaintiffs’ con-stitutional claims against the USPTO andthat the complaint satisfied the pleadingrequirements set forth in Ashcroft v. Iqbal,––– U.S. ––––, 129 S.Ct. 1937, 173 L.Ed.2d868 (2009).

Plaintiffs’ motion for summary judgmentand the cross-motions for summary judg-ment and judgment on the pleadings wereheard and marked fully submitted on Feb-ruary 4, 2010.

II. THE PARTIES AND AMICI

Plaintiff Association for Molecular Pa-thology (‘‘AMP’’) is a not-for-profit scienti-fic society dedicated to the advancement,

practice, and science of clinical molecularlaboratory medicine and translational re-search based on the applications of genom-ics and proteomics. AMP members partic-ipate in basic and translational researchaimed at broadening the understanding ofgene/protein structure and function, dis-ease processes, and molecular diagnostics,and provide clinical medical services forpatients, including diagnosis of breast can-cer. Sobel Decl. ¶¶ 2, 4–5.2

Plaintiff the American College of Medi-cal Genetics (‘‘ACMG’’) is a private, non-profit voluntary organization of clinical andlaboratory geneticists. The Fellows of theACMG are doctoral level medical geneti-cists and other physicians involved in thepractice of medical genetics. With morethan 1300 members, the ACMG’s missionis to improve health through the practiceof medical genetics. In order to fulfill thismission, the ACMG strives to define andpromote excellence in medical geneticspractice and the integration of translation-al research into practice; promote andprovide medical genetics education; in-crease access to medical genetics servicesand integrate genetics into patient care;and advocate for and represent providersof medical genetics services and their pa-tients. Watson Decl. ¶¶ 2, 4–5.

Founded in 1922, plaintiff the AmericanSociety for Clinical Pathology (‘‘ASCP’’) isthe largest and oldest organization repre-senting the medical specialty of pathologyand laboratory medicine. ASCP is a not-for-profit entity organized for scientificand educational purposes and dedicated topatient safety, public health, and the prac-tice of pathology and laboratory medicineand has 130,000 members working as pa-thologists and laboratory professionals.ASCP members design and interpret thetests that detect disease, predict outcome,

2. For purposes of this opinion, references tothe parties’ declarations will be in the format

[Declarant name] Decl. ¶ [paragraph num-ber].


and determine the appropriate therapy forthe patient. The ASCP is recognized forits excellence in continuing professionaleducation, certification of laboratory pro-fessionals, and advocacy. Ball Decl. ¶¶ 2,5.

Plaintiff the College of American Pa-thologists (‘‘CAP’’) is a national medicalsociety representing more than 17,000 pa-thologists who practice anatomic pathologyand laboratory medicine in laboratoriesworldwide. The College’s Commission onLaboratory Accreditation is responsiblefor accrediting more than 6,000 laborato-ries domestically and abroad, and approxi-mately 23,000 laboratories are enrolled inCAP’s proficiency testing programs. It isthe world’s largest association composedexclusively of board-certified pathologistsand pathologists in training worldwide andis widely considered the leader in labora-tory quality assurance. CAP is an advo-cate for high quality and cost-effectivemedical care. Scott Decl. ¶¶ 2, 4–5.

Plaintiff Haig Kazazian, M.D. (‘‘Dr. Ka-zazian’’), is the Seymour Gray Professor ofMolecular Medicine in Genetics in the De-partment of Genetics at the University ofPennsylvania School of Medicine. He is ahuman genetics researcher and the previ-ous chair of the Department. Dr. Kazazi-an and plaintiff Arupa Ganguly, Ph.D.(‘‘Dr. Ganguly’’), designed tests to screenthe BRCA1 and BRCA2 genes in their laband provided screening to approximately500 women per year starting in 1996. Drs.Kazazian and Ganguly ceased theirBRCA1/2 testing in response to cease-and-desist letters from Myriad relating to thepatents-in-suit. Kazazian Decl. ¶¶ 1–5.

Plaintiff Dr. Ganguly is an AssociateProfessor in the Department of Genetics atthe Hospital of the University of Pennsyl-vania. Dr. Ganguly’s work previously in-cluded BRCA1/2 screening for both re-search and clinical purposes. She ceased

BRCA1/2 screening following her receiptof cease-and-desist letters from Myriad ac-cusing her lab of violating the patents-in-suit. Ganguly Decl. ¶¶ 1, 3–5.

Plaintiff Wendy Chung, M.D., Ph.D.(‘‘Dr. Chung’’), is an Associate Professor ofPediatrics and the Herbert Irving Profes-sor of Pediatrics and Medicine in the Divi-sion of Molecular Genetics at ColumbiaUniversity. Dr. Chung is a human geneti-cist whose current research includes re-search on the BRCA1 and BRCA2 genes.Because of the patents-in-suit, Dr. Chungcurrently cannot tell research subjects inher studies the results of their BRCA1/2tests and cannot offer clinical BRCA1/2testing services. Chung Decl. ¶¶ 1–9, 11–13, 16.

Plaintiff Harry Ostrer, M.D. (‘‘Dr. Ostr-er’’), is a Professor of Pediatrics, Patholo-gy and Medicine and Director of the Hu-man Genetics Program in the Departmentof Pediatrics at New York UniversitySchool of Medicine. Dr. Ostrer’s work hasfocused on understanding the genetic basisof development and disease, including dis-orders of sexual differentiation and geneticsusceptibility to breast and prostate cancerand malignant melanoma. Dr. Ostrer isactively engaged in identifying genes thatconvey risk of breast cancer and that maymitigate the effects of mutations in theBRCA1 and BRCA2 genes. Dr. Ostrer isalso the Director of the Molecular GeneticsLaboratory of NYU Medical Center, oneof the largest academic genetic testing lab-oratories in the United States. Because ofthe patents-in-suit, Dr. Ostrer currentlycannot tell research subjects in his studiesthe results of their BRCA1/2 tests andcannot offer clinical BRCA1/2 testing ser-vices. Ostrer Decl. ¶¶ 1–4.

Plaintiff David Ledbetter, Ph.D. (‘‘Dr.Ledbetter’’), is a Professor of Human Ge-netics and Director of the Division of Med-ical Genetics at the Emory University


School of Medicine. Research in his labo-ratory focuses on the molecular character-ization of human developmental disorders.Dr. Ledbetter directs the Emory GeneticsLaboratory which provides testing servicesfor individuals with or at risk for geneticdiseases. Because of the patents-in-suit,Dr. Ledbetter cannot offer comprehensiveBRCA1/2 genetic testing to patients. Led-better Decl. ¶¶ 1–8, 16.

Plaintiff Stephen T. Warren, Ph.D. (‘‘Dr.Warren’’), is the William Patterson TimmieProfessor of Human Genetics, Chairman ofthe Department of Human Genetics, andProfessor of Biochemistry and Professor ofPediatrics at Emory University. He is apast President of the American Society ofHuman Genetics. Dr. Warren supervisesgenetic research at Emory and is responsi-ble for the laboratories at the Emory Ge-netics Laboratory. These laboratorieswould offer BRCA1/2 genetic testing butfor the patents-in-suit. Ledbetter Decl.¶¶ 1, 16.

Plaintiff Ellen Matloff, M.S. (‘‘Ms. Mat-loff’’), is Director of the Yale Cancer Ge-netic Counseling Program. Ms. Matloffadvises women on the desirability of ob-taining an analysis of their genes to deter-mine if the women have the genetic muta-tions that correlate with an increased riskof breast and/or ovarian cancer. If shedetermines that such an analysis is war-ranted and the individual woman concurs,Ms. Matloff arranges for the analysis andthen advises the woman of the significanceof the results. Ms. Matloff would like tohave the option to send patient samples tolaboratories other than Myriad Geneticsfor BRCA1/2 sequencing. Matloff Decl.¶¶ 1–4, 11.

Plaintiff Elsa W. Reich, M.S. (‘‘Ms.Reich’’), is a Professor in the Departmentof Pediatrics at New York University.She is a genetic counselor. She helpswomen decide whether to be tested for

mutations in the BRCA1 and BRCA2genes. If they need testing, she sendssamples to Myriad and explains the resultsfor the women. Ms. Reich would like tohave the option to send patient samples tolaboratories other than Myriad forBRCA1/2 sequencing. Reich Decl. ¶¶ 1–3,8.

Plaintiff Breast Cancer Action (‘‘BCA’’)is a national organization of approximately30,000 members based in San Francisco,California. BCA is dedicated to repre-senting the voices of people affected bybreast cancer in order to inspire and com-pel the changes necessary to end thebreast cancer epidemic. Its members in-clude breast cancer survivors, familymembers of people diagnosed with breastcancer and other people affected by orconcerned about breast cancer. BCA ad-vocates for policy changes directed atachieving prevention, finding better treat-ments, and reducing the incidence ofbreast cancer, provides information aboutbreast cancer to anyone who needs it vianewsletters, web sites, e-mail and a toll-free number, and organizes people to getinvolved in advocacy to advance its policygoals. Brenner Decl. ¶¶ 1–3.

Plaintiff Boston Women’s Health BookCollective, doing business as Our BodiesOurselves (‘‘OBOS’’), is a nonprofit, publicinterest women’s health education, advoca-cy, and consulting organization. OBOSprovides information about health, sexuali-ty and reproduction from a feminist andconsumer perspective. OBOS advocatesfor women’s health and provides informa-tion to members of the public about genet-ic analysis. Norsigian Decl. ¶¶ 1–4.

Plaintiff Lisbeth Ceriani (‘‘Ms. Ceriani’’)is a 43–year–old single mother who wasdiagnosed with cancer in both breasts inMay 2008. Ms. Ceriani is insured throughMassHealth, a Medicaid insurance pro-gram for low-income people. Her oncolo-


gist and genetic counselor recommendedthat she obtain BRCA1 and BRCA2 genet-ic testing because she may need to consid-er further surgery in order to reduce herrisk of ovarian cancer. However, Myriadwill not accept the MassHealth coverage,and Ms. Ceriani is unable to pay the fullcost out-of-pocket. Ceriani Decl. ¶¶ 1–6.

Plaintiff Runi Limary (‘‘Ms. Limary’’) isa 32–year–old Asian–American woman whowas diagnosed with aggressive breast can-cer in 2005. Ms. Limary obtainedBRCA1/2 testing through Myriad and re-ceived the following result: ‘‘genetic vari-ant of uncertain significance.’’ Because ofMyriad’s patents, she is unable to pursuealternative testing options. Limary Decl.¶¶ 1–5.

Plaintiff Genae Girard (‘‘Ms. Girard’’) isa 39–year–old woman who was diagnosedwith breast cancer in 2006. Shortly afterher diagnosis, she obtained BRCA1/2 ge-netic testing from Myriad and tested posi-tive for a deleterious mutation on theBRCA2 gene. She sought a second opin-ion of that test result but learned thatMyriad is the only laboratory in the coun-try that can provide full BRCA1/2 se-quencing. Girard Decl. ¶¶ 1–6.

Plaintiff Patrice Fortune (‘‘Ms. For-tune’’) is a 48–year–old woman who wasdiagnosed with breast cancer in February2009. Ms. Fortune is insured throughMedi–Cal. Her oncologist and geneticcounselor recommended that she obtainBRCA1/2 genetic testing, including thesupplemental testing that is offered byMyriad separate from its standard test,but told her that Myriad would not accepther insurance. Ms. Fortune is unable topay the full cost out-of-pocket. FortuneDecl. ¶¶ 1–5.

Plaintiff Vicky Thomason (‘‘Ms. Thoma-son’’) is a 52–year–old woman who wasdiagnosed with ovarian cancer in 2006.She obtained BRCA1/2 genetic testing

from Myriad in 2007 and was found to benegative for mutations covered by thattest. Her genetic counselor advised herabout additional BRCA1/2 genetic testingoffered by Myriad that looks for otherlarge genetic rearrangements that are notincluded in Myriad’s standard full sequenc-ing test, but informed her that her insur-ance would not cover the full cost of thattest. Ms. Thomason is unable to affordthe extra cost. Thomason Decl. ¶¶ 1–8.

Plaintiff Kathleen Raker (‘‘Ms. Raker’’)is a 41–year–old woman whose mother andmaternal grandmother died from breastcancer. She obtained BRCA1/2 genetictesting from Myriad in 2007 and was foundto be negative for mutations covered bythat test. Her genetic counselor advisedher about additional BRCA1/2 genetic test-ing offered by Myriad that looks for otherlarge DNA rearrangements that are notincluded in Myriad’s standard full sequenc-ing test, but informed her that it wasunclear whether her insurance would coverthe full cost of that test. Ms. Raker isunable to afford the extra cost. RakerDecl. ¶¶ 1–9.

Defendant USPTO is an agency of theCommerce Department of the UnitedStates with its principal office in Alexan-dria, Virginia. USPTO Answer ¶ 27.

Defendant Myriad is a for-profit corpo-ration incorporated in Delaware with itsprincipal place of business in Salt LakeCity, Utah. Myriad is the former co-ownerof several of the patents-in-suit and thecurrent exclusive licensee of the patents-in-suit. Myriad is the sole provider of fullsequencing of BRCA1 and BRCA2 genesin the United States on a commercial ba-sis. Myriad Answer ¶ 28.

The University of Utah Research Foun-dation, whose directors are named as de-fendants in their official capacity, is an


owner or part-owner of each of the pat-ents-in-suit. Myriad Answer ¶ 29.

Amici curiae American Medical Associa-tion, American Society of Human Genetics,American College of Obstetricians and Gy-necologists, American College of Embryol-ogy, and The Medical Society of the Stateof New York are non-profit organizationsrepresenting physicians and medical stu-dents throughout the United States, in-cluding New York; professionals in thefield of human genetics, including re-searchers, clinicians, academicians, ethi-cists, genetic counselors and nurses whosework involve genetic testing; women’shealth care professionals; and embryolo-gists. These amici contend that the pat-ents-in-suit are directed to unpatentablenatural phenomena in violation of Article I,Section 8, Clause 8 of the Constitution, and35 U.S.C. § 101, are unnecessary to pro-mote innovation in genetic research, andviolate medical and scientific ethics.

Amici curiae March of Dimes Founda-tion, Canavan Foundation, Claire AltmanHeine Foundation, Breast Cancer Coali-tion, Massachusetts Breast Cancer Coali-tion, National Organization for Rare Dis-orders, and National Tay–Sachs £ AlliedDiseases Association are non-profit organi-zations dedicated to advancing the treat-ment of a variety of genetic diseases, in-cluding breast cancer, Tay–Sachs, SpinalMuscular Dystrophy, Canavan disease,and other rare genetic disorders. Theseamici contend that Myriad’s patents repre-sent patents on natural phenomena andlaws of nature, thereby restricting futureresearch and scientific progress.

Amici curiae National Women’s HealthNetwork, Asian Communities for Repro-ductive Justice, Center for Genetics andSociety, Generations Ahead, and Pro–Choice Alliance for Responsible Researchare non-profit organizations seeking to im-prove the health of women; promote re-

productive justice; encourage responsibleuse and governance of genetic, reproduc-tive and biomedical technologies; promotepolicies on genetic technologies that pro-tect human rights; promote accountability,safety, and social justice in biomedical re-search from a women’s rights perspective.These amici contend that isolated DNAconstitutes an unpatentable product of na-ture whose patenting harms women bystifling innovation and interfering with pa-tient access to medical testing and treat-ment. These amici also contend that hu-man genes and the information containedtherein constitute part of the common her-itage of humanity, and patenting humangene sequences is contrary to both inter-national law and treatises as well as thepublic trust doctrine.

Amici curiae The International Centerfor Technology Assessment, IndigenousPeople Council on Biocolonialism, Green-peace, Inc., and Council for ResponsibleGenetics are non-profit organizations dedi-cated to assisting the public and policymakers in understanding how technologyaffects society, protecting the cultural heri-tage and genetic materials of indigenouspeoples; addressing global environmentalproblems; and protecting the public inter-est and fostering public debate about thesocial, ethical, and environmental implica-tions of genetic technologies. These amicicontend that the patents-in-suit claim un-patentable products of nature and thatgene patents have significant negative con-sequences, including privatization of genet-ic heritage in violation of fundamental pre-cepts of common heritage, public domain,and the public trust doctrine; creation ofprivate rights of unknown scope and signif-icance; facilitate the exploitation of indige-nous peoples; and violation of patients’rights to informed consent.

Amicus curiae Biotechnology IndustryOrganization (‘‘BIO’’) is the country’s larg-


est biotechnology trade association, repre-senting over 1200 companies, academic in-stitutions, and biotechnology centers in all50 states. BIO members are involved inthe research and development of biotech-nological healthcare, agricultural, environ-mental, and industrial products. BIOmember companies range from start-upbusinesses and university spin-offs to largeFortune 500 corporations. BIO contendsthat patents directed to isolated DNA fallwithin the categories of patent-eligiblesubject matter because they differ ‘‘inkind’’ from naturally-occurring DNA. TheBIO also contends that patents such as theones in dispute here provide incentives forinvestment in biotechnology that promotesthe advancement of science.

Amicus curiae Boston Patent Law Asso-ciation (‘‘BPLA’’) is a non-profit associa-tion of attorneys and other intellectualproperty professionals. BPLA’s membersserve a broad range of clients who rely onthe patent system, including independentinvestors, corporations, investors, and non-profit and academic institutions, such asuniversities and research hospitals.BPLA contends that patents, includingpatents on gene-related inventions, pro-mote innovation by protecting investmentsin the innovation process. It further con-tends that the patents-in-suit satisfy therequirements of 35 U.S.C. § 101 as well asthe Constitution.

Amicus curiae Generic Alliance (‘‘GA’’)is a not-for-profit, tax-exempt health advo-cacy organization founded in 1986 (as theAlliance for Genetic Support Groups). Itbrings together diverse stakeholders thatcreate novel partnerships in advocacy.By integrating individual, family, and com-munity perspectives to improve healthsystems, Genetic Alliance seeks to revolu-tionize access to information to enabletranslation of research into services andindividualized decision-making. GA con-

tends that the wholesale abolition of pat-ents on isolated DNA molecules and iso-lated purified natural substances is legallyuntenable and undesirable as public poli-cy, because it would diminish the promiseof genetic research for patients and nega-tively affect other areas of medicine.

Amicus curiae Rosetta Genomics, Inc. isa wholly owned subsidiary of amicus curiaeRosetta Genomics, Ltd., a molecular diag-nostics company that provides diagnostictests for cancer and which owns severalpatents claiming isolated nucleic acid se-quences. Amicus curiae George MasonUniversity (‘‘George Mason’’) is a publicuniversity located in Virginia. Researchconducted at George Mason has been in-corporated into patent applications cover-ing cancer diagnostics. These amici con-tend that the question of patentability ofhuman gene sequences is appropriatelyleft to Congress; that the patents-in-suitpromote, rather than hinder innovation;and that the challenged patents are lawfulunder 35 U.S.C. § 101 and the Constitu-tion.

Amicus curiae BayBio is an independent,nonprofit 501(c)(6) trade association serv-ing the life sciences industry in NorthernCalifornia, and represents more than 330companies involved in the research anddevelopment of treatments, cures, and di-agnostics. Amicus curiae Celera Corpora-tion is a manufacturer of diagnostic prod-ucts that include gene-based products usedin genetic testing. Amicus curiae The Co-alition for 21st Century Medicine repre-sents some of the world’s most innovativediagnostic technology companies, clinicallaboratories, researchers, physicians, ven-ture capitalists, and patient advocacygroups that share a common mission todevelop advanced diagnostics that improvethe quality of healthcare for patients.Amicus curiae Genomic Health, Inc., is alife sciences company committed to im-


proving the quality of cancer treatmentdecisions through genomics-based clinicallaboratory services and currently offersthe Oncotype DX breast cancer assay,which predicts the likelihood of the recur-rence of specific types of breast cancer andwhether a patient will benefit from certaintreatment strategies. Amicus curiae Qia-gen, N.V. is a leading provider of innova-tive sample and assay technologies andproducts which are considered standardfor use in molecular diagnostics, appliedtesting, and academic and pharmaceuticalresearch and development. Amicus curiaeTarget Discovery, Inc. discovers, validates,and utilizes protein isoforms to improveclinical diagnosis and management of dis-ease. Amicus curiae XDx, Inc., is a molec-ular diagnostics company focused on thediscovery, development and commercializa-tion of non-invasive gene expression test-ing in the areas of transplant medicine andautoimmunity through the use of moderngenomics and bioinformatics technology.These amici contend that patent exclusivi-ty is required for the development of per-sonalized medicine and that the challengedpatents satisfy the requirements of 35U.S.C. § 101 and the Constitution. In ad-dition, the amici contend that the harmalleged by Plaintiffs can be redressedthrough traditional judicial remedies anddo not require a finding that isolated DNAconstitutes unpatentable subject matter.

Amicus curiae Kenneth Chahine, Ph.D.(‘‘Professor Chahine’’), is a Visiting Profes-sor of Law at S.J. Quinney College of Lawat the University of Utah. Professor Chah-ine contends that the scope of the claims-in-suit are sufficiently limited to avoidclaiming products of nature and that theclaims directed to isolated DNA and diag-nostic process satisfy the requirements ofpatentable subject of 156 matter under 35U.S.C. § 101.

Amicus curiae Kevin E. Noonan, Ph.D.(‘‘Dr. Noonan’’), is a patent attorney withMcDonnell Boehnen Hulbert & BerghoffLLP. Dr. Noonan contends that isolatedhuman DNA constitutes patentable subjectmatter and that a ban on patenting isolat-ed human DNA would negatively affectthe development of human therapeutics,the development of personalized medicine,and the scientific research in general.

III. THE FACTS

The facts as set forth in this section aretaken from the parties’ respective state-ments and counterstatements pursuant toLocal Civil Rule 56.1 and the affidavitssubmitted by the parties and amici and arenot in dispute except where noted.

A. The Development of Genetics as aField of Knowledge

The field of genetics—the science of he-redity and variation in living organisms—and the concept of units of heredity thatcould be transmitted from one generationto another originated in the 19th centuryfrom experiments with pea plants conduct-ed by Gregor Mendel. Mendel showedthat certain traits are passed on from par-ent to offspring as discrete entities and donot appear blended in the offspring. Hehypothesized that it was the plant’s geno-type, or assortment of hereditary factors,that determined the plant’s phenotype, orappearance. Mason Decl. ¶ 8. In 1909, thisunit of inheritance was termed a ‘‘gene.’’Yet the gene remained an abstract conceptuntil 1915, when it was shown that genescorresponded to physical spans of chromo-somal material. Mason Decl. ¶ 9.

In 1944, scientists determined that thechemical compound known as deoxyribo-nucleic acid, or DNA,3 served as the carri-

3. Scientists had learned to extract DNA from the body by removing it from the rest of the


er for genetic information by demonstrat-ing that DNA extracted from one strain ofbacteria and transferred to another straincould transfer certain characteristicsfound in the first strain. Oswald Theo-dore Avery, et al., Studies on the Chemi-cal Nature of the Substance InducingTransformation of Pneumococcal Types:Induction of Transformation by a Desox-yribonucleic Acid Fraction Isolated fromPneumococcus Type III, 79 J. Exp. Med.137–158 (1944).

On April 25, 1953, James Watson andFrancis Crick published their determina-tion of the famous double-helix structure ofDNA in the journal Nature. James D.Watson & Francis H.C. Crick, A Structurefor Deoxyribose Nucleic Acid, 171 Nature737–38 (1953). Dr. Crick subsequentlycontributed to the decryption of the genet-ic code and proposed ‘‘the central dogma’’of molecular biology: (1) information isencoded in a segment of DNA, i.e., a gene;(2) transmitted through a molecule calledRNA; and then (3) utilized to direct thecreation of a protein, the building block ofthe body. Mason Decl. ¶ 10.

Our understanding of the DNA con-tained within our cells has since grown atan exponential rate and has included thelandmark completion of the first full-lengthsequence of a human genome, containing25,000 genes, as a result of the work per-formed by the Human Genome Projectfrom 1990 to 2003. Sulston Decl. ¶¶ 11, 22.Access to the information encoded in ourDNA has presented expansive new possi-bilities for future biomedical research andthe development of novel diagnostic andtherapeutic approaches. How this genom-ic information is best harnessed for thegreater good presents difficult questions

touching upon innovation policy, social pol-icy, medical ethics, economic policy, andthe ownership of what some view as ourcommon heritage.

B. Molecular Biology and Gene Se-quencing

An understanding of the basics of molec-ular biology is required to resolve the is-sues presented and to provide the requi-site insight into the fundamentals of thegenome, that is, the nature which is at theheard of the dispute between the parties.What follows represents the standard un-disputed knowledge of those in the field ofmolecular biology as set forth in the par-ties’ 56.1 Statements and expert declara-tions. Citations are also made to two es-tablished texts in the field: Bruce Alberts,et al., Molecular Biology of the Cell (4thed. 2002) (‘‘The Cell’’) and James Watson,et al., Molecular Biology of the Gene (6thed. 2008) (‘‘The Gene’’).

1. DNA

DNA is a chemical molecule composedof repeating chemical units known as ‘‘nu-cleotides’’ or ‘‘bases.’’ DNA is composedof four standard nucleotides: adenine, thy-mine, cytosine, and guanine. As short-hand, scientists denote nucleotides by thefirst letter of the names of their bases:‘‘A’’ for adenine; ‘‘G’’ for guanine; ‘‘T’’ forthymine; and ‘‘C’’ for cytosine. These nu-cleotide units are composed of severalchemical elements, namely carbon, hydro-gen, oxygen, nitrogen, and phosphorus,and are linked together by chemical bondsto form a strand, or polymer, of the DNAmolecule. Kay Decl. ¶¶ 14, 125; LinckDecl. ¶ 70. Although it can exist as asingle strand of nucleotides, DNA typicallyexists as a ‘‘double helix’’ 4 consisting of

cellular material since as early as 1869. RalfDahm, Discovering DNA: Friedrich Miescherand the Early Years of Nucleic Acid Research,122 Human Genetics 565–581, 567–68 (2008).

4. It was the description of this famous ‘‘dou-ble-helix’’ structure that earned Watson andCrick the Nobel Prize.


two intertwined strands of DNA that arechemically bound to each other. Thisstructure is possible because of a propertyof DNA known as ‘‘base pair complemen-tarity’’ or ‘‘base pairing,’’ in which adenineon one strand of DNA always binds tothymine on the other strand of DNA, andguanine on one strand always bind to cyto-sine on the other strand. Kay Decl. ¶ 129.For example, if a portion of one strand ofDNA has the nucleotide sequenceACTCGT, the corresponding section ofDNA on the complementary strand willhave the nucleotide sequence TGAGCA.

Genes are basic units of heredity foundin all living organisms and are responsiblefor the inheritance of a discrete trait. Sul-ston Decl. ¶ 11. In molecular terms, agene is composed of several, typically con-tiguous, segments of DNA. Kay Decl.¶ 142. Each gene is typically thousands ofnucleotides long and usually ‘‘encodes’’ oneor more proteins, meaning it contains theinformation used by the body to producethose proteins. Some of the segments ofDNA within a gene, known as ‘‘exons’’ or‘‘coding sequences,’’ contain sequences nec-essary for the creation of a protein, whileother segments of DNA, known as ‘‘in-trons,’’ are not necessary for the creationof a protein.5 See Mason Decl. ¶ 11; KayDecl. ¶ 151; Schlessinger Decl. ¶ 14.DNA encodes proteins by way of threenucleotide combinations, termed ‘‘codons,’’that correspond to one of twenty aminoacids that constitute the building blocks ofproteins. Sulston Decl. ¶¶ 14–15. For ex-ample, the codon adenine-thymine-guanine(ATG) encodes the amino acid methionine.Kay Decl. ¶ 158. However, because thereare only twenty different amino acids but

64 possible codons that can be derivedfrom combinations of the four DNA nu-cleotides, most amino acids are encoded bymore than one DNA codon. The Gene at37 & Table 2–3.

Together, the approximately 25,000genes in the human body make up thehuman genome.6 The genome, and thegenes within it, are contained within al-most every cell in the human body anddefine physical traits such as skin tone,eye color, and sex, in addition to influenc-ing the development of conditions such asobesity, diabetes, Alzheimer’s disease, andbipolar disorder. Mason Decl, ¶¶ 4–5;Sulston Decl. ¶¶ 10–11.

The linear order of DNA nucleotidesthat make up a polynucleotide, such as agene, is referred to as the ‘‘nucleotide se-quence,’’ ‘‘DNA sequence,’’ or ‘‘gene se-quence.’’ 7 Kay Decl. ¶ 126; SchlessingerDecl. ¶ 19; Linck Decl. ¶ 45; Sulston Decl.¶ 16; Mason Decl. ¶ 13; Chung Decl. ¶ 10.Gene sequences constitute biological infor-mation insofar as they describe the struc-tural and chemical properties of a particu-lar DNA molecule and serve as the cellular‘‘blueprint’’ for the production of proteins.Sulston Decl. ¶ 16; Kay Decl. ¶ 126;Schlessinger Decl. ¶ 19; Linck Decl. ¶¶ 45,46. Genes and the information represent-ed by human gene sequences are productsof nature universally present in each indi-vidual, and the information content of ahuman gene sequence is fixed. Whilemany inventive steps may be necessary toallow scientists to extract and read a genesequence, it is undisputed that the order-ing of the nucleotides is determined by

5. Introns can contain regulatory sequencesthat affect the body’s rate of production of theprotein encoded by a gene. Kay Decl. ¶ 151.

6. Genome is defined as ‘‘[t]he totality of ge-netic information belonging to a cell or an

organism; in particular, the DNA that carriesthis information.’’ The Cell at G:15.

7. By analogy, if a gene is the equivalent of aword, then the nucleotide sequence is theequivalent of the word’s spelling.


nature. Sulston Decl. ¶ 10, 17; OstrerDecl. ¶ 14; Chung Decl. ¶ 25; LedbetterDecl. ¶ 27; Leonard Decl. ¶ 15.

Scientists often use the term ‘‘wild-type’’to refer to the ‘‘normal’’ human gene se-quence, i.e. the sequence of a gene withoutany variations,8 against which individuals’gene sequences are compared. MasonDecl. ¶ 17; Grody Decl. ¶ 46. Variationsin the human genome are very common:aside from identical twins, the genomes ofany two individuals are estimated to haveone to five nucleotide differences for every1000 nucleotides. Mason Decl. ¶ 14; Sul-ston Decl. ¶ 12.

Variations in the human genome, alsoknown as ‘‘mutations,’’ can occur at differ-ent scales. Small scale variations can bemanifested as slight sequence differencesbetween the same genes in different indi-viduals. Thus, for example, if the wild-type sequence of a portion of a gene isrepresented by GACTCG, a variation ofthat sequence might omit the first C (re-sulting in GATCG) or contain an extra Cat that point (resulting in GACCTCG) orreverse the order of two of the letters(e.g., GCATCG). Mason Decl. ¶ 16. Al-ternatively, there can be large scale varia-tions, such as the addition or deletion ofsubstantial chromosomal regions. Thus, aparticular gene may omit several hundredletters at one point or may add severalhundred letters where they do not normal-ly exist in the wild-type gene sequence.

Even larger variations, known as structur-al variants, also can occur, involving thedeletion or duplication of up to millions ofnucleotides. Extra copies or missing cop-ies of the genome that are larger than1000 nucleotides are called ‘‘copy numbervariants’’ (‘‘CNVs’’). Mason Decl. ¶ 15, 18.

Some of these mutations have little orno effect on the body’s processes, whileother mutations, including those that ap-pear to correlate with an increased risk ofparticular diseases, do interfere with thebody’s processes.9 There are also variantsof uncertain significance (‘‘VUS’’): variantswhose effect on the body’s processes, ifany, is currently unknown. Mason Decl.¶ 19; Sulston Decl. ¶ 18; Kay Decl. ¶ 76.

DNA as it is found in the human body—‘‘native DNA’’ or ‘‘genomic DNA’’—ispackaged, along with proteins, into com-plex structures known as chromosomes,which contain the vast majority of thegenes located in the cells of the humanbody. Kay Decl. ¶ 131; Schlessinger Decl.¶ 12. This mixture of DNA and proteinsthat makes up chromosomes is also re-ferred to as chromatin. See The Gene at135. Genes are organized on forty-sixchromosomes (twenty-three of which areinherited from the mother, and twenty-three of which are inherited from the fa-ther) which together constitute the vastmajority of the human genome.10 MasonDecl. ¶ 5. The proteins within the chromo-somes are bound 11 to the DNA molecules

8. At the same time there is an increasingrecognition that the notion of a single‘‘normal’’ gene sequence may not be entire-ly accurate in light of the high frequency ofvariations in a gene’s sequence between in-dividuals. Mason Decl. ¶ 17. For purposesof this opinion, however, genes are treatedas having a single ‘‘normal’’ DNA sequence.

9. The correlation between a particular muta-tion and disease susceptibility is not self-evi-dent from the mutation itself; rather, exten-sive statistical analysis is required to identify

which alterations in the nucleotide sequencecorrelate with a particular medical condition,a process which may take many years. KayDecl. 1190.

10. A very small fraction of human genes arelocated in a cellular organelle known as themitochondria. Kay Decl. ¶ 144; SchlessingerDecl. ¶ 23. Neither party appears to believethat a discussion of mitochondrial DNA bearsmuch relevance to the legal issues presented.

11. The ionic chemical bonds that exists be-tween proteins and DNA molecules differ


and modulate the structure and function ofthe DNA molecules to which they are asso-ciated. Kay Decl. ¶ 131; SchlessingerDecl. ¶ 12; The Cell at 198, 208, Fig. 4–24.This interaction between chromosomalproteins and native DNA is one method bywhich the body establishes which genesare inactive, which genes are active, andthe level of activity. Kay Decl. ¶ 132.Some DNA in the body also undergoeschemical modifications, such as methyla-tion,12 which can affect the level of activityof a gene, but does not affect the nucleo-tide sequence of the gene. Kay Decl.¶ 132; Mason Supp. Decl. ¶ 22.

2. Extracted and purified DNA

Native DNA may be extracted from itscellular environment, including the associ-ated chromosomal proteins, using anynumber of well-established laboratorytechniques. Grody Decl. ¶ 13; LeonardDecl. ¶ 33. A particular segment of DNA,such as a gene, contained in the extractedDNA may then be excised from the ge-nomic DNA in which it is embedded toobtain the purified DNA of interest. KayDecl. ¶¶ 133, 137. DNA molecules mayalso be chemically synthesized in the labo-ratory. Kay Decl. ¶¶ 17, 133, 137.

Although the parties use the term ‘‘iso-lated DNA’’ to describe DNA that isseparated from proteins and other DNAsequences, the term ‘‘isolated DNA’’ pos-sesses a specific legal definition reflectingits use in the patents-in-suit. To avoidany confusion for purposes of this factrecitation, the term ‘‘extracted DNA’’ will

be used to refer to DNA that has beenremoved from the cell and separatedfrom other non-DNA materials in the cell(e.g., proteins); ‘‘purified DNA’’ will beused to refer to extracted DNA whichhas been further processed to separatethe particular segment of DNA of inter-est from the other DNA in the genome;and ‘‘synthesized DNA’’ will be used torefer to DNA which has been synthe-sized in the laboratory.

As noted above, native DNA, unlike pu-rified or synthesized DNA, is not typicallyfound floating freely in cells of the body,but is packaged into chromosomes. KayDecl. ¶¶ 131, 148. However, when DNA iscopied, or replicated, in preparation forcell division, short segments of DNA aredissociated from the chromosomal pro-teins, although they are still containedwithin the cell. Similarly, when a particu-lar portion of DNA is transcribed intoRNA, segments of DNA exist dissociatedfrom the proteins normally bound to it.Mason Supp. Decl. ¶ 23.

Purified or synthesized DNA may beused as tools for biotechnological applica-tions for which native DNA cannot beused. Kay Decl. ¶¶ 134, 138; SchlessingerDecl. ¶ 27. For example, unlike nativeDNA, purified or synthesized DNA may beused as a ‘‘probe,’’ 13 which is a diagnostictool that a molecular biologist uses to tar-get and bind to a particular segment ofDNA, thus allowing the target DNA se-quence to be detectable using standard

from the covalent chemical bonds which holdDNA itself together. See The Cell at 198 (de-scribing DNA in the cell as ‘‘associated withproteins that fold and pack the fine DNAthread into a more compact structure.’’); id.at 208 Fig. 4–24 (demonstrating dissociationof histone proteins from DNA by high saltsolution, indicating lack of covalent bond be-tween DNA and histones).

12. Methylation refers to the addition of asmall chemical group composed of one car-bon atom and three hydrogen atoms (CH3),known as a ‘‘methyl group,’’ to the nucleo-tides of a segment of DNA. See The Cell at430.

13. A probe is a DNA fragment that is usuallybetween 100–1000 nucleotides long. KayDecl. ¶ 135.


laboratory machinery. Kay Decl. ¶ 135;Schlessinger Decl. ¶ 29. Purified or syn-thesized DNA can also be used as a ‘‘prim-er’’ 14 to sequence a target DNA, a processused by molecular biologists to determinethe order of nucleotides in a DNA mole-cule, or to perform polymerase chain reac-tion (‘‘PCR’’) amplification, a process whichutilizes target-DNA specific primers to du-plicate the quantity of target DNA expo-nentially. Critchfield Decl. ¶ 40; KayDecl. ¶ 184.

During this process, the DNA moleculebeing used as a probe or a primer binds,or ‘‘hybridizes,’’ to a specific nucleotidesequence of a DNA target molecule, suchas the BRCA1 or BRCA2 gene. This se-quence-specific binding of two strands ofDNA results from the same base-pairingphenomenon which allows two complemen-tary strands of DNA to form the doublehelix structure. As a result, a strand ofisolated DNA being used as a primer withthe sequence ATGTCG, for example, willbind specifically to the portion of the tar-get DNA molecule containing the nucleo-tide sequence TACAGC. The hybridiza-tion of a primer or probe to a DNA target,such as BRCA1 or BRCA2, results in theformation of a ‘‘hybridization product’’ thateither acts as a substrate for the enzymesused in the sequencing or amplificationreaction or permits the detection of thetarget DNA. See Kay Decl. ¶¶ 138, 183;Schlessinger Decl. ¶ 30; The Gene at 105–06; 113–15.

The utility of purified BRCA1/2 DNAmolecules as biotechnological tools there-fore relies on their ability to selectivelybind to native or isolated BRCA1/2 DNAmolecules, which ability is a function of theisolated DNA’s nucleotide sequence. KayDecl. ¶ 138.

3. RNA

Ribonucleic acid (‘‘RNA’’) is another nu-cleic acid found in cells. Like DNA, anRNA molecule is composed of a combina-tion of four different nucleotides, three ofwhich are the same bases incorporatedinto DNA: adenine, cytosine, and guanine.Unlike DNA, however, RNA utilizes uracilas the fourth nucleotide base, rather thanthymine. In addition, the sugar-phosphatebackbone in RNA is chemically differentfrom the sugar-phosphate backbone ofDNA. Kay Decl. ¶ 170.

The creation of proteins, which do thework of the body, comprises two steps:transcription and translation. Transcrip-tion is the process by which a temporarycopy of a particular DNA sequence, in theform of an RNA molecule, is generated.Mason Decl. ¶¶ 11–12; Kay Decl. ¶¶ 149,150. During transcription, a discrete seg-ment of DNA unwinds itself inside the celland the bases of the DNA molecule act as‘‘clamps’’ that hold the bases of the newlyforming RNA molecule in place while thechemical bonds of its sugar-phosphatebackbone are formed. Kay Decl. ¶ 150.Each nucleotide in the DNA strand corre-sponds to a nucleotide to be incorporatedinto the newly forming RNA molecule:adenine on the DNA molecule binds to andthereby acts as a clamp for RNA nucleo-tide uracil, thymine for adenine, guaninefor cytosine, and cytosine for guanine.Kay Decl. ¶ 150. This newly generatedRNA is termed ‘‘pre-messenger RNA’’ or‘‘pre-mRNA’’ and, like the DNA fromwhich it was generated, contains both in-trons and exons. In a process known as‘‘splicing,’’ the introns are physically cutout of the pre-mRNA by the cell and theremaining RNA segments containing theexons are rejoined, or ‘‘ligated,’’ togetherin consecutive order to form the final

14. A primer is a DNA fragment, usually be-tween 15 and 30 nucleotides long, that binds

specifically to a target DNA sequence. KayDecl. ¶ 183.


‘‘messenger RNA,’’ or ‘‘mRNA.’’ MasonDecl. ¶ 11; Kay Decl. ¶ 151; SchlessingerDecl. ¶ 14. Pre-mRNAs can also undergoa process known as ‘‘alternative splicing,’’in which different combinations of exonsfrom the same pre-mRNA molecule areligated together to yield different finalmRNA products.15 Kay Decl. ¶ 152;Schlessinger Decl. ¶ 14.

During translation, an mRNA moleculeserves as a template for the assembly of aprotein. Kay Decl. ¶ 157. In a processthat parallels the transcription of DNA,the mRNA bases, along with other pro-teins in the cell, serve as clamps to holdthe corresponding amino acids in placewhile the chemical bonds between the indi-vidual amino acids are formed. Kay Decl.¶ 157. The three-nucleotide codons origi-nally found in DNA and copied into mRNAdetermine which amino acids are incorpo-rated into the protein and the order inwhich they are incorporated. Kay Decl.¶ 157.

4. cDNA

Complementary DNA, or ‘‘cDNA,’’ is atype of DNA molecule generated frommRNA during a process known as ‘‘re-verse transcription’’ which is catalyzed bya protein known as ‘‘reverse transcrip-tase.’’ cDNA derives its name from thefact that it is ‘‘complementary’’ to themRNA from which it is produced—that is,each base in the cDNA can bind to thecorresponding base in the mRNA fromwhich it is generated. Kay Decl. ¶ 161.Because it is derived from mRNA, a cDNAmolecule represents an exact copy of oneof the protein coding sequences encodedby the original genomic DNA. Leonard

Decl. ¶ 75. In this respect, cDNA containsthe identical protein coding informationalcontent as the DNA in the body, eventhough differences exist in its physicalform. Mason Decl. ¶ 32.

During reverse transcription, each baseof the mRNA serves as a clamp for itscomplementary nucleotide to be incorpo-rated into the new cDNA molecule whilethe chemical bonds between the nucleo-tides of the cDNA strand are formed.Much like transcription, uracil on themRNA binds to and thereby acts as aclamp for the nucleotide adenine, adeninefor thymine, guanine for cytosine, and cy-tosine for guanine. Kay Decl. ¶ 165. Thesynthesis of cDNA from very long mRNAmolecules, such as BRCA1 and BRCA2,often does not result in a cDNA strandthat is as long as the mRNA chain. KayDecl. ¶ 166.

cDNA is typically generated by scien-tists in a laboratory. Kay Decl. ¶ 164,Linck Decl. ¶ 48. However, naturally oc-curring cDNAs, known as ‘‘pseudogenes,’’exist in the human genome and are struc-turally, functionally, and chemically identi-cal to cDNAs made in the laboratory. Ma-son Supp. Decl. ¶¶ 18–21; Nussbaum Decl.¶¶ 41–42.

cDNA possesses certain structural andfunctional differences from native DNA. Incontrast to most forms of native DNA,cDNA does not contain non-coding intronicsequences because it is derived frommRNA in which the introns have beenremoved. As a result, the production ofproteins from cDNA does not requireRNA splicing, in contrast to the production

15. For example, a pre-mRNA molecule con-taining exons (‘‘E’’) numbered 1–6, with in-trons (‘‘I’’) between each exon whose struc-ture is represented as follows:E1vI1vE2vI2vE3vI3vE4v

I4vE5vI5vE6. After splicing, the intronswould be removed to form an mRNA com-

posed only of exons: E1vE2vE3vE4vE5vE6. On the other hand, the samepre-mRNA molecule might undergo alterna-tive splicing to form final mRNAs with avariety of different exon compositions: forexample, E1vE2vE5; E1vE3vE6; andE1vE4vE6.


of proteins from native DNA as describedabove. Some cDNAs cannot be used toproduce proteins without the addition ofcertain regulatory sequences, althoughother cDNAs possess some of the neces-sary regulatory sequences. cDNAs alsousually contain nucleotides correspondingto the so-called ‘‘poly A tail’’ sequencefound in mRNA, which native DNA doesnot possess. In addition, as mentionedabove, native DNA is often (although notalways) chemically modified in the body,e.g., by methylation, while cDNA generat-ed in the laboratory is not so modified.Kay Decl. ¶¶ 168, 169; Mason Supp. Decl.¶¶ 18–22; Nussbaum Decl. ¶¶ 41–42.cDNA also differs from mRNA in that it isa more stable compound and requires bothtranscription and translation to produceprotein, rather than simply translation, asis the case with mRNA. Kay Decl. ¶ 171.

Much like purified DNA, cDNA can beused as a tool for biotechnological anddiagnostic applications for which nativeDNA cannot be used. Kay Decl. ¶ 162.In addition, a scientist seeking to learnmore about a protein of interest maytransfer a cDNA encoding the protein intoa recipient cell that does not normallyexpress that protein. If the cDNA is op-eratively linked to particular ‘‘promoter’’sequences that initiate transcription fromthe cDNA, the recipient cell will then ex-press the protein of interest. Kay Decl.¶ 163.

5. DNA sequencing

DNA sequencing is the process by whichone ‘‘reads,’’ or determines the ordering ofthe nucleotides within a DNA molecule.Sulston Decl. ¶ 20; Kay Decl. ¶ 138. Inthe context of a gene or a portion of thegenome, sequencing is designed to illumi-nate the information that nature has dic-

tated in that person’s genome, and thesequencing process, by design, does notalter the information content of the nativeDNA sequence. Sulston Decl. ¶ 27; Ma-son Decl. ¶ 32. In that respect, sequenc-ing is analogous to examining somethingthrough a microscope insofar as it makesvisible something that exists in nature butis too small to be seen otherwise. MasonDecl. ¶ 23. Gene sequencing is used indiagnostic testing, such as Myriad’s tests,to determine whether a gene contains mu-tations that have been associated with aparticular condition. Sulston Decl. ¶ 24;Chung Decl. ¶ 10; Swisher Decl. ¶¶ 23–26;Mason Decl. ¶ 21. These mutations, alongwith any association with a propensity todevelop a particular disease, are caused bynature. Chung Decl. ¶ 10; Mason Decl.¶ 20; Sulston Decl. ¶¶ 19, 27; LedbetterDecl. ¶ 26. Therefore, the significance ofany person’s gene sequence, including itsrelationship to any disease, is dictated bynature. Mason Decl. ¶ 32.

Sequencing is often used to identify sin-gle nucleotide substitutions or the inser-tion or deletion of a small number of nu-cleotides in a gene. Swisher Decl. ¶ 23;Kay Decl. ¶ 180. However, even full se-quencing of an entire gene can miss largegenomic rearrangements in which wholesections of the gene have been deleted ormoved to a different part of the genome.Other tests have been developed that bet-ter detect these large rearrangements.Swisher Decl. ¶ 24; Ledbetter Decl. ¶¶ 16–17.

Sequencing native DNA first requiresthat cells of a tissue sample 16 be brokenopen to permit extraction of the DNA con-tained within the cells. Sulston Decl. ¶ 25.The extracted DNA of the entire genome

16. Various types of patient samples can beused, e.g., blood, tumor tissue, or non-tumor

tissue. Kay Decl. ¶ 186.


contains over three billion nucleotides, ofwhich the gene of interest comprises avery small portion. Kay Decl. ¶ 178.BRCA1/2 sequencing by Myriad followsthe typical process for sequencing extract-ed genomic DNA, which begins with ob-taining a sufficient quantity of theBRCA1/2 genomic DNA to permit its se-quencing. Critchfield Decl. ¶ 40.

Under the current state of the art, theonly practical way to obtain a sufficientamount of BRCA1/2 genomic DNA for mu-tation detection purposes is to PCR ampli-fy the genomic DNA in segments. Critch-field Decl. ¶ 40. In order to design thenecessary primers to PCR amplify the cor-rect region of the genome, at least a por-tion of the sequence of the target DNAmolecule must be known. Kay Decl. ¶ 184.Typically, each exon of the BRCA1/2genes, including a small adjacent portionof the flanking introns, is separately ampli-fied by PCR into one or more amplifiedDNA fragments, also called ‘‘amplicons.’’The BRCA1 and BRCA2 genes have atotal of 48 coding exons containing over15,700 nucleotide base pairs. More than50 amplicons are typically produced aspart of Myriad’s BRCA1/2 testing. Critch-field Decl. ¶ 40.

Following PCR amplification of the tar-get DNA, a sequencing reaction is per-formed to determine the nucleotide se-quence of the amplicon. Kay Decl. ¶ 183.As with PCR, at least some of the targetsequence must be known in order to de-sign a primer specific to the target DNAto be sequenced. Kay Decl. ¶¶ 177, 179,183. For this reason, primers that bindonly to specific DNA sequences in theBRCA1 and BRCA2 genes permit the

analysis of a patient’s native DNA se-quence to determine if the nucleotide com-position is the same or different from thenucleotide composition of the normalBRCA1 and BRCA2 gene. Kay Decl.¶ 187. Gene sequencing also sometimesutilizes cDNA as the DNA template.Leonard Decl. ¶ 75.

The techniques required for gene se-quencing are well-known and understoodby scientists skilled in molecular biology,and scientists and clinicians sequence andanalyze genes literally every day. ChungDecl. ¶¶ 10–11; Mason Decl. ¶ 22; HegdeDecl. ¶¶ 6–7. However, because sequenc-ing requires knowledge of the sequence ofa portion of the target sequence, someingenuity and effort is required for theinitial sequencing of a target DNA. SeeKay Decl. ¶ 183; Klein Decl. ¶ 32–34.

C. The Development of the Patents–in–Suit

Breast cancer is the most frequentlydiagnosed cancer worldwide and is theleading cause of cancer death for women inBritain and the second leading cause ofcancer death for women in the UnitedStates. Parthasarathy Decl. ¶ 8.17 Ovariancancer is the eighth most common cancerin women and causes more deaths in theWestern world than any other gynecologiccancer. Swisher Decl. ¶ 10.

Throughout the 1980s, organizationsdedicated to breast cancer awareness be-gan efforts to increase public and govern-mental awareness of the breast cancer epi-demic. In 1991, the U.S. Department ofDefense created a research program de-voted to breast cancer research. Over theyears this funding has grown from less

17. Dr. Parthasarathy has researched the de-velopment of genetic testing for breast andovarian cancer in the United States and Brit-ain and has interviewed over 100 individualsinvolved in the process, including research

scientists, officials at research institutions,health care professionals, patent office offi-cials, bioethicists, and journalists. Parthasar-athy Decl. ¶ 6.


than $90 million during the fiscal year 1990to more than $2.1 billion during the fiscalyear 2008. Parthasarathy Decl. ¶ 10.

Throughout the 1980s, scientists fromthe United States, England, France, Ger-many, Japan, and other countries soughtto be the first to identify DNA nucleotidesequences associated with breast cancer.Parthasarathy Decl. ¶ 11. In 1989, variousEuropean and American research labora-tories participated in the InternationalBreast Cancer Linkage Consortium (the‘‘Consortium’’), and in 1990, a group ofresearchers led by Mary–Claire King (‘‘Dr.King’’) at the University of California,Berkeley, published a landmark paperdemonstrating for the first time that agene linked to breast cancer, whose se-quence was unknown but which was laterdesignated Breast Cancer SusceptibilityGene 1 (BRCA1 ), was located on a regionof chromosome 17. See Jeff M. Hall, etal., Linkage of Early–Onset FamilialBreast Cancer to Chromosome 17q21, 250Science 1684–89 (1990); ParthasarathyDecl. ¶ 11. Soon afterwards, research in-tensified as teams around the world, in-cluding groups led by Dr. King, Dr. MarkSkolnick (‘‘Dr. Skolnick’’) (co-founder ofMyriad), and Dr. Michael Stratton (‘‘Dr.Stratton’’) (Institute for Cancer Research,London (‘‘ICR’’)), focused in on this regionof the genome in an attempt to be the firstto determine the DNA sequence ofBRCA1. Parthasarathy Decl. ¶ 11.

Dr. Skolnick, a 1968 economics graduateof the University of California, Berkeley,had become interested in the application ofdemography to the study of genetics whiledoing research for his Ph.D. in genetics,which he received from Stanford Universi-ty in 1975. While reconstructing genealo-gies in Italy, he met three Mormons whowere microfilming parish records and fromwhom he learned of the resources of theUtah Genealogical Society in Salt Lake

City. Thereafter, in 1973, after an inquiryfrom the organizers of a cancer center atthe University of Utah, Dr. Skolnick sug-gested linking the Utah Mormon Genealo-gy with the Utah Cancer Registry. Tofurther this effort, a familial cancerscreening clinic was established and a pro-gram for mapping genes was developed.Skolnick Decl. ¶¶ 7, 11, 12.

Following publication of the Kinggroup’s study relating to BRCA1 in the fallof 1990, Dr. Skolnick and his collaboratorsconcluded that additional resources wouldbe required to compete with the team ofDr. Francis Collins, which had received asubstantial grant from the National Insti-tutes of Health (‘‘NIH’’), Skolnick Decl.¶¶ 13, 14, and in 1991 Myriad was foundedby Dr. Skolnick and a local venture capitalgroup interested in genetics. Myriad re-ceived 55 million in funding in 1992, $8million in 1993, and 59 million in 1994.Skolnick Decl. ¶ 16.

Locating the BRCA1 gene relied on theuse of linkage analysis, in which correla-tions between the occurrence of cancer andthe inheritance of certain DNA markersamong family members were used to iden-tify, or ‘‘map,’’ the physical location of, theBRCA1 gene within the human genome.See 8282 patent, col. 7:39–52. Once thephysical location had been narrowed downto a sufficiently small region of the ge-nome, Myriad was able to directly analyzethe sequence of the DNA in this regionand identify the nucleotides comprising theBRCA1 gene. See 8282 patent, col. 7:53–8:7. Successful linkage analysis requireslarge and genetically informative families,or kindreds, and detailed family informa-tion, such as detailed genealogical records,are an important component to this analy-sis. Shattuck Decl. ¶¶ 10, 13; 8282 patent,col. 8:16–29.

In September 1994, the group at Myri-ad, along with researchers from the Na-


tional Institute for Environmental HealthSciences (‘‘NIEHS’’) (a subdivision of theNIH), the University of Utah, McGill Uni-versity, and Eli Lilly and Company an-nounced that they had sequenced theBRCA1 gene. See Yoshio Miki, et al., AStrong Candidate for the Breast and Ova-rian Cancer Susceptibility Gene BRCA1,266 Science 66–71 (1994). In addition tofunding the six NIEHS researchers whoparticipated in the identification ofBRCA1, the NIH had also provided ap-proximately $2 million in funding to theUniversity of Utah.18 See id. at 71 n. 52;Parthasarathy Decl. ¶ 18. According toone analysis, the NIH contributed one-third of the funding for the identificationof BRCA1. Parthasarathy Decl. ¶ 18.

A dispute subsequently arose betweenMyriad and the NIH over the NIEHSscientists’ exclusion as co-inventors on theBRCA1 patents. Parthasarathy Decl. ¶ 19.The NIH maintained that its scientists hadconducted some of the most importantwork leading up to the sequencing of thegene, including identifying the sequencesof two of the BRCA1 gene fragments andassembling the complete BRCA1 sequence.Id. Myriad agreed to include the names ofthe NIEHS researchers as inventors on itspatent application and pay inventors’ roy-alties, although no payments appear tohave been made as of 2005. Id.

Following the isolation of BRCA1, scien-tists continued to search for a second genealso believed to be linked with breast andovarian cancer.19 Parthasarathy Decl.¶ 12. Myriad collaborated with several re-search groups, including scientists at theUniversity of Laval in Quebec, Canada, theHospital for Sick Children in Toronto,Canada, and the University of Pennsylva-

nia in their search for this second gene. Italso collaborated with a team of research-ers led by Dr. Stratton at the ICR which,in November 1995, identified a mutation inbreast cancer patients that appeared to belocated in the as-yet unpublished BRCA2gene. Dr. Stratton ended the collabora-tion with Myriad upon learning of Myriad’splans to patent the BRCA2 gene sequence.Sulston Decl. ¶ 30.

On December 21, 1995, Myriad filed forpatents on the BRCA2 gene in both theU.S. and Europe. Tavtigian Decl. ¶ 5. Thenext day, the Stratton group published itsidentification of the BRCA2 gene in thejournal Nature, and Myriad submitted thesequence of BRCA2 to GenBank, an inter-national depository of gene sequence infor-mation. Parthasarathy Decl. ¶ 12; Tavti-gian Decl. ¶ 9; Richard Wooster, et al.,Identification of the Breast Cancer Sus-ceptibility Gene BRCA2, 378 Nature 789–92 (1995). Subsequent analysis of theBRCA2 sequence from the Stratton groupindicated that while they had correctly se-quenced the primary portion of theBRCA2 gene, their published sequencehad errors in both ends of the BRCA2gene. Tavtigian Decl. ¶¶ 7–10. Nonethe-less, the consensus among the scientificcommunity is that the Stratton group,rather than Myriad, was the first to se-quence the BRCA2 gene. ParthasarathyDecl. ¶ 13.

The isolation of the BRCA1/2 genes re-quired considerable effort on the part ofMyriad and its collaborators as well asingenuity in overcoming technical obstaclesassociated with the isolation process.However, the process and techniques usedwere well understood, widely used, and

18. According to the description of author as-sociations, the first and second authors of thepaper were associated with the University ofUtah.

19. The same positional cloning approach uti-lized to isolate the BRCA1 gene was relied onto isolate the BRCA2 gene. Tavtigian Decl.¶ 4.


fairly uniform insofar as any scientist en-gaged in the search for a gene would likelyhave utilized a similar approach. Partha-sarathy Decl. ¶ 19; Tavtigian Decl. ¶ 13.

D. Application of the Patents–in–Suit

Mutations in the BRCA1/2 genes corre-late with an increased risk of breast andovarian cancer. Women with BRCA1 andBRCA2 mutations face up to an 85% cu-mulative risk of breast cancer, as well asup to a 50% cumulative risk of ovariancancer. Love Decl. ¶ 10; ParthasarathyDecl. ¶ 9. In addition, among the 10–15%of ovarian cancer cases that are inheritedgenetically, 80% of women diagnosed un-der the age of 50 carry mutations in theirBRCA1 genes and 20% carry mutations intheir BRCA2 genes. The women with in-herited BRCA1 mutations have a 40–52%cumulative risk of ovarian cancer by thetime they reach 70 years old. For womenwith inherited BRCA2 mutations, the riskis approximately 15–25%. Swisher Decl.¶ 11. Male carriers of mutations are alsoat an increased risk for breast and pros-tate cancer. Love Decl. ¶ 10.

The existence of BRCA1/2 mutations istherefore an important consideration inthe provision of clinical care for breastand/or ovarian cancer. A patient will notonly learn of her risk for hereditary breastand ovarian cancer, but also can gain infor-mation that may be useful in determiningprevention and treatment options. Thisinformation is useful for women who arefacing difficult decisions regarding wheth-er or not to undergo prophylactic surgery,hormonal therapy, chemotherapy, and oth-er measures. Swisher Decl. ¶ 12; LoveDecl. ¶ 11. Testing results for theBRCA1/2 genes can be an important factorin structuring an appropriate course of

cancer treatment, since certain forms ofchemotherapy can be more effective intreating cancers related to BRCA1/2 muta-tions. Swisher Decl. ¶ 13; Love Decl.¶ 18.

1. Myriad’s BRCA1/2 testing

Myriad offers multiple forms ofBRCA1/2 testing to the general public.Its standard test, called ComprehensiveBRACAnalysis, originally only consisted ofthe full sequencing of the BRCA1/2 genes.Swisher Decl. ¶¶ 29–30; Reich Decl. ¶ 10;Parthasarathy Decl. ¶ 26; Critchfield Decl.¶ 49. In 2002, Myriad supplemented itsfull sequencing analysis with a large rear-rangement panel (‘‘LRP’’) for detectingfive common large rearrangement muta-tions which is now included in the Compre-hensive BRACAnalysis. Critchfield Decl.¶¶ 49, 51. In 2006, Myriad began offeringa supplemental test to ComprehensiveBRACAnalysis called the BRACAnalysisRearrangement Test (‘‘BART’’), which, ac-cording to Myriad, can detect virtually alllarge rearrangement mutations in theBRCA1 and BRCA2 genes.20 SwisherDecl. ¶¶ 29–30; Reich Decl. ¶ 10; Partha-sarathy Decl. ¶ 26; Critchfield Decl. ¶ 51.

2. Funding for Myriad’sBRCA1/2 tests

The Myriad tests are available to clini-cians and patients at a cost of over $3000per test. In 2008, the total cost to Myriadof providing these tests was $32 millionwith resulting revenues of $222 million.See Myriad Genetics, Inc., Annual Report(Form 10–K), at 27 (Aug. 28, 2008). InOntario, where the regional public health-care plan is ignoring Myriad’s patent, thetesting for breast cancer is performed fora third of Myriad’s cost. See CBC News,Ontario to Offer New Genetic Test forBreast, Ovarian Cancer (Jan. 8, 2003),

20. Myriad also offers other more limitedforms of BRCA1/2 genetic testing. Swisher

Decl. ¶¶ 29–30; Reich Decl. ¶ 10; Parthasara-thy Decl. ¶ 26


available at http: //www.cbc.ca/health/story/2003/01/06/test denetic030106.html.

Plaintiffs have noted several instanceswhere women have been unable to obtainfunding for all of Myriad’s testing services.For example, Myriad refused to processMs. Ceriani’s sample because it did notaccept coverage by Ms. Ceriani’s insurancecarrier. Unable to pay for Myriad’s tests,and unable to find scholarship programs tofund her testing, Ms. Ceriani has not beentested. Ceriani Decl. ¶¶ 5–7. Ms. For-tune’s insurance carrier is not accepted byMyriad, and Ms. Fortune is also unable topay the full out-of-pocket cost of Myriad’stest. Fortune Decl. ¶ 5.

Myriad’s BART test is not covered by anumber of insurers, and unless a patient isone of a limited number of ‘‘high riskpatients’’ who meet certain clinical criteriaestablished by Myriad, a patient must payan extra fee for BART testing. SwisherDecl. ¶¶ 29–30; Reich Decl. ¶ 10; Partha-sarathy Decl. ¶ 26; Critchfield Decl. ¶ 52.As a result of the cost of BART testing,the test is unavailable to women whowould otherwise choose to utilize the test.Swisher Decl. ¶¶ 30–31; Reich Decl. ¶ 10.For example, Ms. Raker is unable to af-ford the extra cost for BART testing andhas not been tested for large genomic re-arrangements, despite the advice of hergenetic counselor. Raker Decl. ¶¶ 7–11.Similarly, Ms. Thomason has been unableafford the BART testing recommended byher genetic counselor. Thomason Decl.¶¶ 6–9.

Myriad has pursued Medicaid coveragefor years, but has been unable to secure‘‘participating provider’’ status in 25 stateswhich would allow it to offer testing to thatstate’s Medicaid patients. Myriad also hasa financial assistance program which pro-vides free testing to low-income and unin-sured patients who meet certain economicand clinical requirements. In addition,

Myriad provides free testing to indepen-dent non-profit institutions. In particular,Ms. Ceriani may be eligible to receiveBRACAnalysis testing at no chargethrough the non-profit organization CancerResource Foundation, for which Myriadhas provided free testing since 2009. Rus-coni Decl. ¶¶ 4–6; Critchfield Decl. ¶ 33;Ogaard Decl. ¶¶ 4–6. Currently, 90% ofthe tests Myriad performs are covered byinsurance at over 90% of the test cost.Critchfield Decl. ¶¶ 32, 33, 52, 53.

A number of researchers, clinicians, andmolecular pathologists have the personnel,equipment, and expertise to sequence andanalyze genes, including the BRCA1 andBRCA2 genes, at a lower cost than Myri-ad’s testing. Kazazian Decl. ¶¶ 8, 11;Matloff Decl. ¶ 12; Ostrer Decl. ¶¶ 8–9;Ledbetter Decl. ¶¶ 16–18. For example,the BRCA1/2 testing previously conductedby the Yale DNA Diagnostics Laboratoryand the University of Pennsylvania Genet-ic Diagnostic Laboratory (‘‘GDL’’) cost lessthan what Myriad charges, and testing byOncorMed, a one-time competitor, wascheaper than Myriad’s testing. MatloffDecl. ¶ 7; Kazazian Decl. ¶ 8; Parthasara-thy Decl. ¶ 24. However, on a ‘‘cost perexon’’ basis, Myriad’s BRACAnalysis testcosts less than testing for other genesperformed by the GDL at the Universityof Pennsylvania and Drs. Ledbetter andWarren at Emory University. See infra;Critchfield Decl. ¶ 35.

3. Myriad’s enforcementof the patents-in-suit

During the mid–to–late–1990s, Drs. Ka-zazian and Ganguly offered, for a fee,screening services for BRCA1 mutationsthrough the GDL at the University ofPennsylvania. Kazazian Decl. ¶ 4; Gangu-ly Decl. ¶ 3. The screening methodologyutilized by Drs. Kazazian and Ganguly dif-fered from the testing method used byMyriad, but involved using isolated DNA


encoding BRCA1 or BRCA2. KazazianDecl. ¶ 9; Parthasarathy Decl. ¶ 23. Atsome point during this period, Dr. Skolnickadvised Dr. Kazazian that Myriad plannedto stop the BRCA1/2 testing being con-ducted at the GDL. Kazazian Decl. ¶ 6. OnMay 29, 1998, Myriad offered Dr. Kazaziana collaborative license in connection withthe 8473, 8999, 8001, 8282, and 8441 patents.Ganguly Decl. Ex. 2. However, the licensecovered only single mutation tests andmultiple mutation panels of up to fourmutations to allow for testing of patients ofAshkenazi Jewish descent. Ganguly Decl.¶ 5. Myriad subsequently sent cease anddesist letters to Dr. Kazazian and the Uni-versity of Pennsylvania. On August 26,1998, OMelveny & Myers LLP gave noticeto Dr. Kazazian of infringement in theabsence of a license. Ganguly Decl. Ex. 3.Myriad subsequently sued the Universityof Pennsylvania in November 1998 for in-fringement of the patents-in-suit. SeeMyriad Genetics v. Univ. of Pennsylva-nia, 2:98–cv–00829 (D.Utah) (filed Novem-ber 19, 1998). On June 10, 1999, Myriad’sgeneral counsel, Christopher Wright, senta letter to the University of Pennsylvaniaseeking written assurances that Dr. Kaza-zian and the University of Pennsylvaniahad ceased BRCA1/2 clinical testing. Gan-guly Decl. Ex. 4. This demand was re-peated in a September 22, 1999 letter fromMyriad to the University of Pennsylvania.Ganguly Decl. Ex. 6.

As a result of Myriad’s efforts to enforceits patents against the University of Penn-sylvania, the GDL no longer conductsBRCA1/2 screening for research or as partof its clinical practice. Kazazian Decl. ¶ 5;Ganguly Decl. ¶¶ 8–9; Parthasarathy Decl.¶ 28. However, sometime between 1999and 2000, Dr. Critchfield, on behalf ofMyriad, informed Dr. Kazazian that he isfree to conduct academic research on theBRCA1/2 genes, including sequencing the

genes and detecting mutations in thegenes. Critchfield Decl. ¶ 22.

In May 1998, Myriad offered Dr. Ostrera license agreement to conduct diagnosticBRCA1/2 genetic testing. The proposedlicense would permit Dr. Ostrer to conductsingle mutation tests and multiple muta-tion panels (up to four mutations) for pa-tients of Ashkenazi Jewish descent only.Dr. Ostrer declined the offer as too narrowto allow him to perform any meaningfulBRCA1/2 testing. Ostrer Decl. ¶ 7.

On September 15, 1998, Myriad also no-tified Dr. Barbara Weber (‘‘Dr. Weber’’), aprincipal investigator on the Cancer Ge-netics Network Project (‘‘CGNP’’) spon-sored by the National Cancer Institute(‘‘NCI’’), that Myriad’s patent positionmight impact research sponsored by NCI.As a result of that letter, the GDL at theUniversity of Pennsylvania ceased con-ducting BRCA1/2 analysis for Dr. Weber.Ganguly Decl. ¶ 12, Ex. 7. According toMyriad, the GDL’s involvement in CGNPwas to provide DNA testing on BRCA1/2genes for a fee, similar to the activity ofany commercial core lab. Critchfield Decl.¶ 21. In September 1999, Myriad also re-quested that Georgetown University, oneof the other cancer centers participating inthe CGNP, to cease sending genetic sam-ples to the GDL for BRCA1/2 analysis.Ganguly Decl. ¶ 13.

In December 2000, the director of theYale DNA Diagnostics Lab received acease and desist letter concerningBRCA1/2 genetic testing being conductedby the lab. As a result of the letter, thelab ceased BRCA1/2 genetic testing. Mat-loff Decl. ¶ 7. In 2005, Dr. Matloff soughtpermission from Myriad for the Yale DNADiagnostics Lab to conduct screening formutations caused by large rearrange-ments, which Myriad was not conductingat the time. Her request was denied.Matloff Decl. ¶ 8.


Myriad was also involved in a series oflawsuits in the late 1990s against On-cormed, another company undertakingBRCA-related testing, regarding patentsthat covered various aspects of the BRCA1gene sequence. Parthasarathy Decl. ¶ 27.Myriad eventually purchased Oncormed’spatents and testing services in 1998. Id.

E. Disputed Issues1. The impact of Myriad’s patents

on BRCA1/2 testing

According to Plaintiffs, Myriad’s patentsand its position as the sole provider ofBRCA1/2 testing has hindered the abilityof patients to receive the highest-qualitybreast cancer genetic testing and has im-peded the development of improvements toBRCA1/2 genetic testing. Plaintiffs firstnote deficiencies in the genetic testing ser-vices offered by Myriad, alleging that inthe several years prior to the addition ofthe LRP, the testing done by Myriad didnot reveal all known mutations in theBRCA1/2 genes or utilize known methodol-ogies that would have revealed these addi-tional mutations.21 Chung Decl. ¶ 19;Matloff Decl. ¶ 8; Swisher Decl. ¶ 26;Ledbetter Decl. ¶ 16; Parthasarathy Decl.¶ 29. As a result, Myriad’s test may havereported false negative results during thisperiod. Plaintiffs also cite a study publish-ed in 2006 in the Journal of the AmericanMedical Association that concluded that12% of those from high risk families withbreast cancer and with negative test re-sults from Myriad carried cancer-predis-posing genomic deletions or duplications inone of those genes. Swisher Decl. ¶¶ 25–26. Plaintiffs also note that the sensitivityand specificity of the BART test has notbeen validated by comparing the results ofBART testing with Multiplex Ligation De-

pendent Probe Amplification (‘‘MLPA’’)testing commonly used by researchers.Swisher Decl. ¶¶ 32, 33.

According to Plaintiffs, other labs are ina position to offer more comprehensivetesting than Myriad’s standard testing ser-vices and would use newer testing methodswith improved testing quality and efficien-cy. These labs would also include largerearrangement testing after a negativetest result is received from full sequencing.Ledbetter Decl. ¶¶ 17–18; Chung Decl.¶ 18; Ostrer Decl. ¶ 9. In addition, labswould perform genetic testing on tumorspecimens preserved in paraffin from de-ceased family members, which Myriaddoes not regularly perform even though,according to Plaintiffs, such testing canoften provide valuable genetic informationfor living relatives and is often necessaryfor accurate test interpretation. ChungDecl. ¶ 24.

According to Myriad, however, its fullsequencing test has been recognized as the‘‘gold standard’’ for BRCA1/2 mutationtesting, and it continues to improve itstesting process. Critchfield Decl. ¶ 37.Myriad contends that it researched anddeveloped a commercially viable high qual-ity test for detecting large rearrangementsas soon as it and the research communityrecognized the need for such testing, andcontinues work towards a test capable ofdetecting all large rearrangement muta-tions, including extremely rare ones.Critchfield Decl. ¶¶ 49, 50. According toMyriad, BRCA1/2 studies conducted byoutside researchers confirmed that theBART test exhibited superior performanceover other methods for mutation detection,including the MLPA kit often used by

21. For example, the Myriad test received byMs. Thomason, Ms. Raker, and Ms. Limarydid not look for all known large rearrange-

ments in the BRCA genes. Thomason Decl.¶ 6; Raker Decl. ¶¶ 7–8; Limary Decl. ¶ 7.


academic researchers.22 Critchfield Decl.¶ 51.

According to Plaintiffs, the lack of in-dependent BRCA1/2 analysis also under-mines the ability of the scientific commu-nity to determine the meaning of VUSresults, which are reported disproportion-ately for members of minority groups,and whose significance would be more ex-tensively analyzed by other labs. ChungDecl. ¶ 20–21; Ostrer Decl. ¶ 12; MatloffDecl. ¶ 9. Myriad, however, asserts that ithas undertaken significant efforts to de-termine the clinical importance of VUSsby establishing an in-house review com-mittee for variant classification and devel-oping a systematic approach to providingclinical interpretations for detected se-quence variants based on generally ac-cepted scientific data and analysis of itsown database. In addition, clarificationof any VUS previously reported to a pa-tient is immediately provided to the pa-tient and her doctor. According to Myri-ad, the VUS reporting rate has decreasedmarkedly, with a 50% decrease in majorethnic groups between 2002 and 2006,and a total of 850 VUSs for about 21,000patients have been clarified, including 502VUSs for 13,127 patients since the begin-ning of 2008. Myriad also asserts that ithas made critical data available to re-searchers to assist in the analysis ofVUSs and which have the potential of im-proving the diagnostic testing for othergenes. Critchfield Decl. ¶¶ 57–59.

Plaintiffs contend that as a result of thepatents-in-suit, BRCA1/2 genetic testing isone of the very few tests performed as

part of breast cancer care and preventionfor which a doctor or patient cannot get asecond confirmatory test done through an-other laboratory. Love Decl. ¶ 12. Inparticular, women who receive a positiveresult cannot confirm the lab’s findings orseek a second opinion on the interpretationof those results.23 Ledbetter Decl. ¶ 23;Ostrer Decl. ¶ 11. According to Myriad,absent any doubts regarding the accuracyof the original test, resequencing the pa-tient’s genes by another laboratory wouldbe an unnecessary waste of resources, andMyriad has never prohibited a second in-terpretation of the results of its diagnostictests. Critchfield Decl. ¶ 64; Reilly Decl.¶¶ 54, 55. In addition, there are multiplelaboratories available to conduct confirma-tory BRCA1/2 testing pursuant to patentlicenses granted by Myriad, including boththe University of Chicago Genetic ServicesLaboratories and Yale DNA DiagnosticLaboratories. Critchfield Decl. ¶ 62.That confirmatory testing, however, is lim-ited to the confirmation of certain, specificpositive test results; the remaining typesof positive test results as well as all nega-tive test results are excluded from suchtesting services. Matloff Decl. ¶¶ 9, 10.

Whether the patents at issue impact thetesting for BRCA1/2 mutations favorablyor unfavorably is an issue of factual dis-pute not resolvable in the context of theinstant motions.

2. The impact of gene patents onthe advancement of science

and medical treatment

There exists a deep disagreement be-tween the parties concerning the effects of

22. In addition, Myriad states that the MLPAkit is for research use only, is not approvedfor clinical testing by the FDA, and is incapa-ble of detecting certain smaller rearrange-ments. Critchfield Decl. ¶¶ 49, 50.

23. For example, Ms. Girard sought but wasunable to obtain confirmatory testing of herMyriad test results that indicated the presence

of a deleterious mutation in her BRCA2 gene.A second opinion would also be important forher immediate family’s screening options.Girard Decl. ¶¶ 4–9. Similarly, Ms. Cerianiand Ms. Fortune would both want a secondopinion concerning their BRCA1/2 status be-fore taking major surgical steps. CerianiDecl. ¶¶ 9, 11; Fortune Decl. ¶ 7.


gene patents on the progression of scienti-fic knowledge.

According to Plaintiffs, data sharing isthe key to the future of genetic discoveriesand bioinformatics, and gene patents im-pede research aimed at identifying the roleof genes in medical conditions. SulstonDecl. ¶¶ 36, 38. Plaintiffs assert that thisunderstanding has wide acceptance, notingthat from the beginning of the HumanGenome project,24 most scientists and evensome private companies recognized the im-portance of keeping the genome freelyavailable to all. For example, in 1994, thepharmaceutical company Merck funded amassive drive to generate gene sequencesand place them into public databases,thereby making them difficult to patent.Sulston Decl. ¶¶ 22, 29. In 1996, a groupof 50 of the most prominent geneticistswho were involved with the sequencing ofthe human genome adopted the Bermudaprinciples which included the mandate thatall ‘‘human genome sequence informationshould be freely available and in the publicdomain in order to encourage research anddevelopment and to maximize its benefit tosociety.’’ Sulston Decl. ¶ 33. The prolifer-ation of intellectual property rights direct-ed to genetic material has also been postu-lated to contribute to a phenomenondubbed ‘‘the tragedy of the anti-commons,’’in which numerous competing patentrights held by independent parties pre-vents any one party from engaging in pro-ductive innovation. See, e.g., Michael A.Heller & Rebecca S. Eisenberg, Can Pat-ents Deter Innovation? The Anticom-mons in Biomedical Research, 280 Science698 (1998) (citing Michael A. Heller, TheTragedy of the Anticommons: Property inthe Transition from Marx to Markets, 111Harv. L. Rev. 621 (1998)).

According to Dr. Fiona Murray (‘‘Dr.Murray’’), who received a grant to re-search the impact of gene patenting onscientific research and commercialization,4382 of the 23,688 genes listed in the data-base of the National Center for Biotech-nology Information (‘‘NCBI’’)—nearly 20%of human genes—are explicitly claimed asUnited States intellectual property. Mur-ray Decl. ¶ 6. After devising a study togauge the impact of gene patenting onpublic knowledge that utilized the time lagbetween publication of papers on a genesequence and the issuance of a patentclaiming that gene sequence, Dr. Murrayconcluded that the Myriad patents havenegatively impacted the public knowledgeof the BRCA1 and BRCA2 genes by 5–10%. Murray Decl. ¶¶ 7–15, 20.

Plaintiffs have cited other studies todemonstrate the chilling effect of gene pat-ents on the advancement of both geneticresearch and clinical testing. A survey oflaboratory directors in the United Statesconducted by Dr. Mildred Cho (the ‘‘Chostudy’’) found that 53% decided not todevelop a new clinical test because of agene patent or license, and 67% believedthat gene patents decreased their ability toconduct research. Cho Decl. ¶ 10. Thiscorrelated with a study conducted by theAmerican Society of Human Genetics thatreported that 46% of respondents felt thatpatents had delayed or limited their re-search. Cho Decl. ¶ 11. The Cho studyalso revealed that of those who stoppedperforming a clinical test because of agene patent or license, the largest numberstopped doing BRCA1 and BRCA2 testing(with the same number having stoppedApolipoprotein E testing). Cho Decl. ¶ 16.Specifically, the survey found that ninelabs had ceased performing BRCA1/2 ge-

24. The Human Genome Project was an inter-national project initiated in 1990 with the aimof sequencing an entire human genome and

in which Sir John Sulston, a Nobel laureate,actively participated. Sulston Decl. ¶¶ 5, 22.


netic testing as a result of the patents-in-suit. In addition to labs that have ceasedperforming BRCA1/2 genetic testing, labshave avoided or refrained from developingtests for BRCA1 and BRCA2 as a result ofthe patents held by Myriad. Ostrer Decl.¶ 6; Ledbetter Decl. ¶¶ 14–16. Studies ofother gene patents have also revealed thatlabs frequently stop developing or offeringclinical tests for disease as a result of genepatents. For example, a purportedly validscientific survey of labs in the UnitedStates found a 26% drop in the number oflabs performing testing for hemochromato-sis as a result of gene patents. Cho Decl.¶¶ 18–20.

Researchers, clinicians, and pathologistsare aware that Myriad has sent cease anddesist letters in connection with the pat-ents-in-suit and that Myriad prohibits clin-ical testing of the BRCA1/2 genes. Kaza-zian Decl. ¶¶ 5–11; Ganguly Decl. ¶¶ 4–14;Chung Decl. ¶ 15; Hegde Decl. ¶ 10; Mat-loff Decl. ¶¶ 5–7; Ostrer Decl. ¶¶ 4–7;Swisher Decl. ¶ 28; Hubbard Decl. ¶¶ 7–8;Kant Decl. ¶ 4; Ledbetter Decl. ¶ 13;Reich Decl. ¶¶ 3, 5; Parthasarathy Decl.¶¶ 28–31. Myriad also does not permitresearchers to tell patients involved in re-search the results of their BRCA1/2 test-ing, leading physicians involved in breastcancer care and research unable to meettheir ethical obligations to provide genetictest results to research subjects, when re-quested. Ostrer Decl. ¶ 10; Chung Decl.¶ 13, 14. In addition to the direct benefitsto the patient of knowing the results oftheir testing, such disclosure would alsoprovide valuable insights into patient be-havior that would enhance patient care.Ostrer Decl. ¶ 10. The AMA has alsoexpressed its belief that the ‘‘[t]he use ofpatents TTT or other means to limit theavailability of medical procedures placessignificant limitation on the disseminationof medical knowledge, and is therefore un-ethical.’’ American Medical Association,

Opinion 9.095–The Use of Patents andOther Means to Limit Availability of Medi-cal Procedures, (adopted June 1995), avail-able at http://www.amaassn.org/ama/pub/physician-resources/medical-ethics/ code-medical-ethics/opinion9095.shtml. In addi-tion, others have argued that human genesare the common heritage of mankindwhose use should not be restricted by pat-ent grants. See, e.g., Pilar A. Ossorio, TheHuman Genome as Common Heritage:Common Sense or Legal Nonsense?, 35J.L. Med. & Ethics 425, 426 (2007); Melis-sa L. Sturges, Who Should Hold PropertyRights to the Human Genome? An Ap-plication of the Common Heritage of Hu-mankind, 13 Am. U. Int’l L.Rev. 219, 245(1997); Barbara Looney, Should Genes BePatented? The Gene Patenting Contro-versy: Ethical and Policy Foundations ofan International Agreement, 26 Law &Pol’y Int’l Bus. 231 (1994); Hubert Curien,The Human Genome Project and Patents,254 Science 1710, 1710–12 (1991).

According to Plaintiffs, Myriad has with-held critical data concerning genetic pre-disposition to breast cancer from theBreast Cancer Information Core (‘‘BIC’’),an international, open access online data-base that is a central repository for infor-mation about the BRCA1/2 genes and theirgenetic variants. The BIC facilitates theidentification of deleterious mutations (i.e.those associated with a higher risk of can-cer), provides a mechanism to collect anddistribute data about genetic variants, andplays an important role in helping to eluci-date the significance of those variantsthrough its collection of data. SwisherDecl. ¶¶ 15, 17, 18; Chung Decl. ¶ 22;Ostrer Decl. ¶ 13. Although the value ofthe BIC comes from the amount and quali-ty of data provided by the scientific com-munity, Myriad, according to Plaintiffs,has not contributed any data to BIC in thepast two years. Sulston Decl. ¶ 36; Swish-


er Decl. ¶¶ 19–21; Ostrer Decl. ¶¶ 12–13;Chung Decl. ¶¶ 21–22; Ledbetter Decl.¶ 20.

Plaintiffs also assert that gene patentsimpede the development of improved ge-netic testing. For example, as new se-quencing technologies offer the possibilityof faster and less expensive sequencing ofa patient’s genes, patents on one or moregenes may impede scientists’ ability to de-velop a comprehensive test for complexdiseases or provide a person with an analy-sis of his or her entire genome. SulstonDecl. ¶ 38; Ledbetter Decl. ¶ 24. In addi-tion, Plaintiffs assert that gene patentsinterfere with the ability of physicians andresearchers to investigate complex dis-eases. For example, BRCA1/2 may beassociated with cancers other than breastand ovarian cancer, but so long as thepatents on these genes remain, no one willbe able to include these genes in tests forother disease predispositions. LedbetterDecl. ¶¶ 24–25. Gene patents similarly im-pede the development and improvement oftests for diseases by geneticists. Ledbet-ter Decl. ¶¶ 14–15. Plaintiffs also assertthat allowing only a single lab to offertesting means that the one lab dictates thestandards for patient care in testing forthat disease; in contrast, patient care ispromoted when more than one lab offers aparticular genetic test, utilizing differentmethodologies, since this can ensure thequality of the testing and accuracy of thetest results. Chung Decl. ¶ 23; LedbetterDecl. ¶ 23; Reich Decl. ¶¶ 9, 11; OstrerDecl. ¶ 11; Parthasarathy Decl. ¶ 31.

Plaintiffs further assert that gene pat-ents are not necessary to create incentivesfor initial discoveries or the developmentof commercial applications, including diag-nostic tests. Cho Decl. ¶ 25; LeonardDecl. ¶¶ 20–21. Patents have not beennecessary for the rapid introduction of ge-netic testing, as evidenced by genetic test-

ing that has been offered prior to theissuance of a patent. Cho Decl. ¶ 21. Insupport of this assertion, Plaintiffs cite astudy of gene patents issued in the UnitedStates for genetic diagnostics that showedthat 67% of these patents were issued fordiscoveries funded by the U.S. govern-ment. Cho Decl. ¶ 22. Similarly, anotherstudy showed that 63% of patents on genesequences resulted from federally sup-ported research. Leonard Decl. ¶ 22. Aspreviously noted, the NIH provided $2million in research grants to the Universi-ty of Utah, or approximately one-third ofthe total funding, for the identification ofthe BRCA1 sequence. ParthasarathyDecl. ¶ 18.

Myriad has contested these assertionsand disputes the idea that patenting ofisolated human DNA conflicts with theadvancement of science. According toMyriad, the quid pro quo of the patentsystem is that inventors, in exchange for alimited period of patent exclusivity, mustprovide a sufficient description of the pat-ented invention so that others may im-prove upon it. Reilly Decl. ¶ 24; DollDecl. ¶ 44. Furthermore, according toMyriad, its policy and practice has beenand still is to allow scientists to conductresearch studies on BRCA1 and BRCA2freely, the result of which has been thepublication of over 5,600 research paperson BRCA1 and over 3,000 research paperson BRCA2, representing the work of over18,000 scientists. Critchfield Decl. ¶¶ 3,13; Li Decl. ¶¶ 3–6; Baer Decl. ¶¶ 3–6;Parvin Decl. ¶¶ 3–6; Sandbach Decl. ¶¶ 3–7.

According to Myriad, patents on isolatedDNA, including the patents-in-suit, actual-ly promote research and advance clinicaldevelopment to the benefit of patients.Reilly Decl. ¶¶ 38, 43; Critchfield Decl.¶¶ 2–18, 65, 68; Linck Decl. ¶¶ 27–28, 71,73; Tavtigian Decl. ¶¶ 14–17; Doll Decl.


¶¶ 45–46; Schlessinger Decl. ¶¶ 31–32.Myriad has contended that gene patentsare essential for obtaining capital invest-ment in the development and commerciali-zation of technological breakthroughs.Linck Decl. ¶¶ 27, 28; Reilly Decl. ¶ 16;Doll Decl. ¶ 46. In support, Myriad hascited a survey published in 2009 by theBIO of 150 biotechnology member compa-nies in the therapeutic and diagnostichealthcare industry stating that the major-ity of companies (61%) generally in-li-censed projects that are in the pre-clinicalor Phase ¶ stage of development, and thusstill require substantial R & D investmentand commercialization risk by the licensee.A substantial majority (77%) of the respon-dents without approved products indicatedthat they expect to spend 5–15 years andover $100 million developing a commercialproduct. Myriad asserts that these expen-ditures dwarf any initial research fundingby the federal government. Reilly Decl.¶ 22. In particular, Myriad notes that asignificant amount of private investmentled to its identification of the BRCA1 andBRCA2 sequences, with the expectation ofpatent protection providing an incentive tofund the research into the determination ofthe gene sequences. Skolnick Decl. ¶¶ 14–16. Therefore, Myriad asserts that absentthe promise of a period of market exclusiv-ity provided by patents and the infusion ofventure and risk capital derived therefrom,companies such as Myriad that capitalizeon innovation simply would not be createdand their products would not be brought tomarket or the clinic. Reilly Decl. ¶¶ 18,34, 51, 52, 62; Critchfield Decl. ¶¶ 67, 68;Linck Decl. ¶ 73.

Myriad also notes that it has made over20,000 submissions to the BIC database,

making it the largest contributor to thedatabase. It has also published the larg-est clinical series of mutation risk in theBRCA1/2 genes based on its testing dataand has tabulated and posted the data onMyriad’s website, where it is freely avail-able to researchers throughout the world.Critchfield Decl. ¶¶ 11, 12.

According to Myriad, the majority ofacademic researchers operating laborato-ries (as opposed to Clinical LaboratoryImprovement Amendments (‘‘CLIA’’)—certified laboratories) do not believe thatthey should share test results with sub-jects outside of the standard clinical set-ting. Reilly Decl. ¶¶ 57–59.

As the declarations submitted by theparties make clear, there exists a sharpdispute concerning the impact of patentsdirected to isolated DNA on genetic re-search and consequently the health of soci-ety. As with the dispute concerning theeffect of the patents-in-suit on BRCA1/2genetic testing, the resolution of these dis-putes of fact and policy are not possiblewithin the context of these motions.

IV. THE PATENTS

A. Summary of the Patents

The subjects of this declaratory judg-ment action are fifteen claims contained inseven patents issued by the USPTO: 25

claims 1, 2, 5, 6, 7, and 20 of U.S. patent5,747,282 (the ‘‘8282 patent’’); claims 1, 6,and 7 of U.S. patent 5,837,492 (the ‘‘8492patent’’); claim 1 of U.S. patent 5,693,473(the ‘‘8473 patent’’); claim 1 of U.S. patent5,709,999 (the ‘‘8999 patent’’); claim 1 ofU.S. patent 5,710,001 (the ‘‘8001 patent’’);claim 1 of U.S. patent 5,753,441 (the ‘‘8441

25. The USPTO granted these patents pursuantto a formal written policy that permits thepatenting of ‘‘isolated and purified’’ DNA en-coding human genes and pursuant to a prac-tice that permits such DNA patents and the

patenting of correlations created by naturebetween natural elements of the body and apredisposition to disease. See Utility Examina-tion Guidelines, 66 Fed. Reg. 1,093 (Jan. 5,2001).


patent’’); and claims 1 and 2 of U.S. patent6,033,857 (the ‘‘8857 patent’’).26

The claims-in-suit may be divided intotwo types of claims: composition claimsand method, or process, claims. Indepen-dent claim 1 of the 8282 patent is represen-tative of the group of composition claimsand claims:

An isolated DNA coding for a BRCA1polypeptide, said polypeptide having theamino acid sequence set forth in SEQID NO:2.

This claim is therefore directed to an iso-lated DNA molecule possessing a nucleo-tide sequence that translates into theBRCA1 protein. Because most aminoacids can result from the translation ofmore than one DNA codon, multiple DNAsequences correspond to the nucleotide se-quence claimed by this claim. Claim 2 ofthe 8282 patent is dependent on claim 1 butcontains an additional limitation that iden-tifies the specific BRCA1 nucleotide se-quence of the claimed DNA.27 Claims 5 and

6 of the 8282 patent are directed to frag-ments as short as 15 nucleotides of theDNA molecules claimed in claims 1 and 2of the 8282 patent.28 Finally, claim 7 of the8282 patent and claim 1 of the 8473 patentare directed to isolated DNA possessingone of the specified mutant BRCA1 genesequences.29

Claims 1, 6, and 7 of the 8492 patent arealso composition claims covering isolatedDNA molecules containing certain speci-fied nucleotide sequences relating to theBRCA2 gene. Claim 1 is directed to anisolated DNA molecule encoding theBRCA2 protein.30 Like claim 1 of the 8282patent, claim 1 of the 8492 patent is direct-ed to multiple possible DNA sequences asa result of the redundancy of the DNAcodons. Claim 6 of the 8492 patent, how-ever, is considerably broader than claim 1and is directed to any DNA nucleotideencoding any mutant BRCA2 protein thatis associated with a predisposition tobreast cancer.31 Claim 7 of the 8492 pat-

26. For purposes of understanding what theclaim terms would have meant to a person ofordinary skill in the art at the time of theapplication for the patents, an applicationdate of August 1994 is presumed for the 8282,88473, 8999, 8001, and 8441 patents and De-cember 1995 for the 8492 and 8857 patents.

27. Claim 2 of the 8282 patent reads: ‘‘Theisolated DNA of claim 1, wherein said DNAhas the nucleotide sequence set forth in SEQID NO:1.

28. Claim 5 of the 8282 patent claims: ‘‘Anisolated DNA having at least 15 nucleotides ofthe DNA of claim 1.’’

Claim 6 of the 8282 patent reads: ‘‘An isolatedDNA having at least 15 nucleotides of theDNA of claim 2.’’

29. Claim 7 of the 8282 patent reads: ‘‘Anisolated DNA selected from the group consist-ing of: (a) a DNA having the nucleotide se-quence set forth in SEQ ID NO:1 having T atnucleotide position 4056; (b) a DNA havingthe nucleotide sequence set forth in SEQ IDNO:1 having an extra C at nucleotide position

5385; (c) a DNA having the nucleotide se-quence set forth in SEQ ID NO:1 having G atnucleotide position 5443; and (d) a DNA hav-ing the nucleotide sequence set forth in SEQID NO:1 having 11 base pairs at nucleotidepositions 189–199 deleted.’’

Claim 1 of the 8473 patent reads: ‘‘An isolatedDNA comprising an altered BRCA1 DNA hav-ing at least one of the alterations set forth inTables 12A, 14, 18 or 19 with the proviso thatthe alteration is not a deletion of four nucleo-tides corresponding to base numbers 4184–4187 in SEQ. ID. NO:1.’’

30. Claim 1 of the 8492 patent reads: ‘‘Anisolated DNA molecule coding for a BRCA2polypeptide, said DNA molecule comprising anucleic acid sequence encoding the aminoacid sequence set forth in SEQ ID NO:2.’’

31. Claim 6 of the 8492 patent reads: ‘‘Anisolated DNA molecule coding for a mutatedform of the BRCA2 polypeptide set forth inSEQ ID NO:2, wherein said mutated form ofthe BRCA2 polypeptide is associated with sus-ceptibility to cancer.’’


ent depends on claim 6, but is restricted tothe mutated forms of the BRCA2 nucleo-tide sequence set forth in the specifica-tion,32 As a result of the breadth of thesecomposition claims, they reach isolatedBRCA1/2 DNA obtained from any humanbeing.

Claim 1 of the 8999 patent is representa-tive of the group of method claims. Itclaims:

A method for detecting a germline alter-ation in a BRCA1 gene, said alterationselected from a group consisting of thealterations set forth in Tables 12A, 14,18, or 19 in a human which comprisesanalyzing a sequence of a BRCA1 geneor BRCA1 RNA from a human sampleor analyzing a sequence of BRCA1cDNA made from mRNA from said hu-man sample with the proviso that saidgermline alteration is not a deletion of 4nucleotides corresponding to base num-bers 4184–4187 of SEQ ID NO:1.

Thus, claim 1 of the 8999 patent covers theprocess of identifying the existence of cer-

tain specific mutations in the BRCA1 geneby ‘‘analyzing’’ the sequence of the BRCA1DNA, RNA, or cDNA made from BRCA1RNA obtained from a human sample.

Most of the remaining method claims-in-suit are similarly structured and directedto the comparison of gene sequences.Claim 1 of the 8001 patent claims a methodfor determining whether a human tumorsample contains a mutation in the BRCA1gene by ‘‘comparing’’ the sequence of theBRCA1 gene from the tumor with thesequence of the BRCA1 gene from a non-tumor sample from the same person.33

Claim 1 of the 8441 patent and claim 1 ofthe 8857 are both directed to the sameprocess, differing only as to whether theclaimed method is directed to BRCA1(8441) or BRCA2 (8857). Both of theseindependent claims are directed to the pro-cess of determining whether an individualhas inherited an altered BRCA1 or BRCA2gene by ‘‘comparing’’ the individual’sBRCA1 or BRCA2 gene sequence with thewild-type BRCA1 or BRCA2 gene se-quence.34 Claim 2 of the 8857 patent cov-

32. Claim 7 of the 8492 patent reads: ‘‘Theisolated DNA molecule of claim 6, whereinthe DNA molecule comprises a mutated nu-cleotide sequence set forth in SEQ IDcNO:1.’’

33. Claim 1 of the 8001 patent reads: ‘‘A meth-od for screening a tumor sample from a hu-man subject for a somatic alteration in aBRCA1 gene in said tumor which comprisesgene comparing a first sequence selectedform [sic] the group consisting of a BRCA1gene from said tumor sample, BRCA1 RNAfrom said tumor sample and BRCA1 cDNAmade from mRNA from said tumor samplewith a second sequence selected from thegroup consisting of BRCA1 gene from a non-tumor sample of said subject, BRCA1 RNAfrom said nontumor sample and BRCA1cDNA made from mRNA from said nontumorsample, wherein a difference in the sequenceof the BRCA1 gene, BRCA1 RNA or BRCA1cDNA from said tumor sample from the se-quence of the BRCA1 gene, BRCA1 RNA orBRCA1 cDNA from said nontumor sample

indicates a somatic alteration in the BRCA1gene in said tumor sample.’’

34. Claim 1 of the 8441 patent reads: ‘‘A meth-od for screening germline of a human subjectfor an alteration of a BRCA1 gene whichcomprises comparing germline sequence of aBRCA1 gene or BRCA1 RNA from a tissuesample from said subject or a sequence ofBRCA1 cDNA made from mRNA from saidsample with germline sequences of wild-typeBRCA1 gene, wild-type BRCA1 RNA or wild-type BRCA1 cDNA, wherein a difference inthe sequence of the BRCA1 gene, BRCA1RNA or BRCA1 cDNA of the subject fromwild-type indicates an alteration in theBRCA1 gene in said subject.’’ Claim 1 of the8857 patent claims: ‘‘A method for identifyinga mutant BRCA2 nucleotide sequence in asuspected mutant BRCA2 allele which com-prises comparing the nucleotide sequence ofthe suspected mutant BRCA2 allele with thewild-type BRCA2 nucleotide sequence, where-in a difference between the suspected mutant


ers a method for determining whether anindividual has a predisposition for breastcancer by ‘‘comparing’’ the individual’sBRCA2 gene sequence with the knownwild-type BRCA2 gene sequence.35

Finally, claim 20 of the 8282 patentclaims a method for determining the effec-tiveness of a potential cancer therapeuticcomprising growing cells carrying an al-tered BRCA1 gene known to cause cancerin the presence and absence of a potentialcancer therapeutic, comparing the growthrates of the cells, and concluding that aslower growth rate in the presence of thepotential therapeutic indicates that it isindeed a cancer therapeutic.36

B. Construction of the Claims 37

1. Legal standard

[1] Before considering the patent-eligi-bility of a patent claim, the disputed termsin the claims must be construed in orderensure the scope of the claims is accurate-ly assessed. See, e.g., Datamize, LLC v.Plumtree Software, Inc., 417 F.3d 1342,1354 (Fed.Cir.2005) (‘‘[A] utility patentprotects ‘any new and useful process, ma-chine, manufacture, or composition of mat-

ter, or any new or useful improvementthereof,’ 35 U.S.C. § 101 (2000), the scopeof which is defined by the patent’s writtenclaims.’’). Courts are charged with inter-preting disputed claim terms as a matterof law. Markman v. Westview Instru-ments, Inc., 517 U.S. 370, 384–85, 116 S.Ct.1384, 134 L.Ed.2d 577 (1996).

[2] In interpreting the meaning ofclaim terms, ‘‘words of a claim are general-ly given their ordinary and customarymeaning’’ to a person of ordinary skill inthe art at the time of invention (i.e., theeffective filing date of the patent applica-tion). Phillips v. AWH Corp., 415 F.3d1303, 1312–13 (Fed.Cir.2005) (internal cita-tions and quotation marks omitted). ‘‘Im-portantly, the person of ordinary skill inthe art is deemed to read the claim termnot only in the context of the particularclaim in which the disputed term appears,but in the context of the entire patent,including the specification.’’ Id. at 1313.Thus, the Federal Circuit has emphasizedthe importance of ‘‘intrinsic’’ evidence inclaim construction: the words of the claimthemselves, the written description in thepatent’s specification, and, when necessary,

and the wild-type sequences identifies a mu-tant BRCA2 nucleotide sequence.’’

35. Claim 2 of the 8857 patent reads: ‘‘A meth-od for diagnosing a predisposition for breastcancer in a human subject which comprisescomparing the germline sequence of theBRCA2 gene or the sequence of its mRNA in atissue sample from said subject with thegermline sequence of the wild-type BRCA2gene or the sequence of its mRNA, whereinan alteration in the germline sequence of theBRCA2 gene or the sequence of its mRNA ofthe subject indicates a predisposition to saidcancer.’’

36. Claim 20 of the 8282 patent reads: ‘‘Amethod for screening potential cancer thera-peutics which comprises: growing a trans-formed eukaryotic host cell containing an al-tered BRCA1 gene causing cancer n the

presence of a compound suspected of beinga cancer therapeutic, growing said trans-formed eukaryotic host cell in the absence ofsaid compound, determining the rate ofgrowth of said host cell in the presence ofsaid compound and the rate of growth ofsaid host cell in the absence of said com-pound and comparing the growth rate ofsaid host cells, wherein a slower rate ofgrowth of said host cell in the presence ofsaid compound is indicative of a cancer ther-apeutic.’’

37. In addition to the claim terms discussedbelow, the parties also dispute the properinterpretation of the method claims—i.e.,whether they may be construed to encompasscertain transformative steps. Because this is-sue is broader in scope than simple claimterm definition, it is addressed infra in Sec-tion VII.D.


the history of the patent application’s pros-ecution before the USPTO. Id. at 1314–17.

[3] The process of claim constructionbegins with the language of the claimsthemselves. The language of the claim iswhat the patentee chose to use to ‘‘ ‘partic-ularly point[ ] out and distinctly claim[ ]the subject matter which the applicant re-gards as his invention.’ ’’ Id. at 1311–12(quoting 35 U.S.C. § 112, ¶ 2). Thus, ‘‘theclaims themselves provide substantialguidance as to the meaning of particularclaim terms.’’ Id. at 1314. In addition tothe particular claim being examined, thecontext provided by other claims may behelpful as well. ‘‘For example, the pres-ence of a dependent claim that adds aparticular limitation gives rise to a pre-sumption that the limitation in question isnot present in the independent claim.’’ Id.at 1314–15.

[4, 5] Claim language must also beread in the context of the specification.Id. at 1315. As the Federal Circuit hasmade clear, ‘‘claims, of course, do notstand alone. Rather, they are part of ‘afully integrated written instrument,’ con-sisting principally of a specification thatconcludes with the claims.’’ Id. (quotingMarkman v. Westview Instruments, Inc.,52 F.3d 967, 978 (Fed.Cir.1995)). ‘‘Forthat reason, claims ‘must be read in viewof the specification, of which they are apart.’ ’’ Id. (quoting Markman, 52 F.3d at979). The specification ‘‘is always highlyrelevant to the claim construction analysis.Usually it is dispositive; it is the singlebest guide to the meaning of a disputedterm.’’ Id. (quoting Vitronics Corp. v.Conceptronic, Inc., 90 F.3d 1576, 1582(Fed.Cir.1996)). Moreover, when the pat-entee ‘‘act[s] as his or her own lexicogra-pher’’ and includes an explicit definition ofa claim term in the specification, that defi-nition is dispositive over any ordinary

meaning. Id. at 1319 (internal citation andquotation marks omitted); see also DigitalBiometrics, Inc. v. Identix, Inc., 149 F.3d1335, 1344 (Fed.Cir.1998).

In relying on the specification to inter-pret claim terms, the Federal Circuit hasalso ‘‘repeatedly warned against confiningthe claims’’ to the embodiments describedin the specification. Phillips, 415 F.3d at1323. The mistake of ‘‘reading a limitationfrom the written description into theclaims’’ is ‘‘one of the cardinal sins ofpatent law.’’ Id. at 1320 (quoting SciMedLife Sys., Inc. v. Advanced CardiovascularSys., Inc., 242 F.3d 1337, 1340 (Fed.Cir.2001)).

Courts may also utilize the prosecutionhistory which ‘‘consists of the completerecord of the proceedings before the PTOand includes the prior art cited during theexamination of the patent TTTT [T]heprosecution history can often inform themeaning of the claim language by demon-strating how the inventor understood theinvention and whether the inventor limit-ed the invention in the course of prosecu-tion, making the claim scope narrowerthan it would otherwise be.’’ Id. at 1317(internal citations omitted). However, theprosecution history ‘‘often lacks the clarityof the specification and thus is less usefulfor claim construction purposes.’’ Id.

[6] Lastly, courts may rely on extrinsicevidence such as dictionaries, treatises,and expert testimony, which may serve toprovide a source of ‘‘accepted meaning ofterms used in various fields of science andtechnology,’’ or by providing ‘‘backgroundon the technology at issue.’’ Id. at 1317–18. However, such ‘‘extrinsic’’ evidence is‘‘less significant than the intrinsic record indetermining the legally operative meaningof the claim language.’’ Id. at 1317 (inter-nal citations and quotation marks omitted).The use of extrinsic evidence may not be


used to contradict the meaning of theclaim terms as evidenced by the intrinsicevidence. Id. at 1317–19; see also BiagroW. Sales, Inc. v. Grow More, Inc., 423F.3d 1296, 1302 (Fed.Cir.2005).

2. Resolution of the disputedclaim terms

a. ‘‘DNA’’ and ‘‘isolated DNA’’

The parties approach the terms ‘‘DNA’’and ‘‘isolated DNA’’ from opposing per-spectives.38 Plaintiffs contend that theterm ‘‘DNA’’ means ‘‘a sequence of nucleicacids, also referred to as nucleotides’’ andtherefore constitutes a ‘‘nucleotide se-quence’’ or a ‘‘polynucleotide.’’ Pl. Br. at10.39 Myriad disputes Plaintiffs’ definitionof ‘‘DNA’’ insofar as Plaintiffs’ definitionsuggests that the term ‘‘DNA’’ refersmerely to information, that is, ‘‘a descrip-tion of the linear order of nucleotide unitsthat make up the polynucleotide.’’ MyriadBr. at 15. Myriad instead argues that‘‘DNA’’ refers to ‘‘a real and tangible mole-cule, a chemical composition made up ofdeoxyribonucleotides linked by a phospho-diester backbone.’’ Myriad Br. at 14.

[7] As its name implies, DNA, or deox-yribonucleic acid, is an acid—a tangible,chemical compound. As Myriad correctlynotes, the specifications make clear that‘‘DNA,’’ as used in the patents, refers to

the physical manifestation of the acid, onethat may be ‘‘substantially separated fromother cellular components which naturallyaccompany a gene.’’ 8473 patent, col. 19:8–9; 8282 patent, col. 19:10–11; 8492 patent,col. 17:64–65. Despite the description ofthe term ‘‘DNA’’ set forth in the briefs,this understanding of the meaning of‘‘DNA’’ is shared by both Plaintiffs’ andMyriad’s declarants. See Kay ¶ 125;Linck ¶ 45; Schlessinger ¶ 12; Grody ¶ 10;Leonard ¶ 30.

[8] The term ‘‘isolated DNA’’ is de-fined by Plaintiffs as ‘‘a fragment of DNAsubstantially separated from other cellularcomponents and other DNA.’’ Pl. Br. at 10.Myriad disputes Plaintiffs’ definition inso-far as it implies that fragments of DNAexist free-floating in the cell, separatefrom other cellular components, such asproteins and the other DNA in the chro-mosome. Myriad Br. at 16. The patentspecifications expressly define ‘‘isolatedDNA’’ as a DNA molecule ‘‘which is sub-stantially separated from other cellularcomponents which naturally accompany anative human sequence [such as] humangenome sequences and proteins’’ and ‘‘in-cludes recombinant or cloned DNA isolatesand chemically synthesized analogs or ana-logs biologically synthesized by heterolo-gous systems.’’ 8473 patent, col. 19:6–15;

38. The degree to which the parties actuallydisagree on the meaning of the discussedclaim terms is unclear; however, to the extentsome disagreement has been noted by theparties, this section seeks to resolve them.

39. For purposes of this opinion, ‘‘Pl. Br.’’refers to Plaintiffs’ Memorandum of Law inSupport of Motion for Summary Judgment;‘‘Myriad Br.’’ refers to Myriad Defendants’Memorandum of Law (1) in Support of TheirMotion for Summary Judgment and (2) inOpposition to Plaintiffs’ Motion for SummaryJudgment; ‘‘Pl. Reply’’ refers to the Memo-randum of Law (1) in Further Support ofPlaintiffs’ Motion for Summary Judgment

Against All Defendants and (2) in Oppositionto the Myriad Defendants’ Motion for Sum-mary Judgment and (3) in Opposition to De-fendant United States Patent and TrademarkOffice’s Motion for Judgment on the Plead-ings; ‘‘Myriad Reply’’ refers to Myriad Defen-dants’ Memorandum in Reply to Plaintiffs’Opposition to Myriad Defendants’ Motion forSummary Judgment; and ‘‘USPTO Reply’’ re-fers to the Reply Memorandum of Law inFurther Support of Defendant United StatesPatent and Trademark Office’s Motion forJudgment on the Pleadings and in Oppositionto Plaintiffs’ Motion for Summary Judgment.


8282 patent, col. 19:8–18; 8492 patent, col.17:62–18:5.

‘‘Isolated DNA’’ is therefore construedto refer to a segment of DNA nucleotidesexisting separate from other cellular com-ponents normally associated with nativeDNA, including proteins and other DNAsequences comprising the remainder of thegenome, and includes both DNA originat-ing from a cell as well as DNA synthesizedthrough chemical or heterologous biologi-cal means.

b. ‘‘BRCA1’’ and ‘‘BRCA2’’

Plaintiffs define the term ‘‘BRCA1’’ as‘‘a particular fragment of DNA found onchromosome 17 that relates to a person’spredisposition to develop breast and ovari-an cancer.’’ Pl. Br. at 11. Similarly,Plaintiffs define the term ‘‘BRCA2’’ as ‘‘aparticular fragment of DNA found onchromosome 13 that relate[s] to a person’spredisposition to develop breast and ovari-an cancer.’’ Pl. Br. at 14. As with Plain-tiffs’ proposed definition of ‘‘isolatedDNA,’’ Myriad argues that these defini-tions are inconsistent with the patents’ def-inition of ‘‘BRCA1’’ and ‘‘BRCA2’’ as ‘‘can-cer-predisposing gene[s], some alleles ofwhich cause susceptibility to breast andovarian cancers’’ because they suggest thatthe BRACl and BRCA2 genes are notintegrated into a chromosome, but are bro-ken, detached, or otherwise easily removedfrom their respective chromosomes, Myri-ad Br. at 16.

The specifications of the patents-in-suitdefine the terms ‘‘BRCA1’’ and ‘‘BRCA2’’as ‘‘a human breast cancer predisposinggene TTT some alleles of which cause sus-ceptibility to cancer, in particular breastand ovarian cancer.’’ 8282 patent, col.4:33–36; see also 8282 patent, col. 1:22–23;8492 patent, col. 1:20–21, 4:28–29. Fur-ther, neither party disputes that ‘‘genes’’refer to segments of DNA incorporatedinto chromosomes.

‘‘BRCA1’’ is therefore construed to referto a human gene, normally integrated intochromosome 17, some alleles of whichcause susceptibility to breast and ovariancancer. Similarly, ‘‘BRCA2’’ is construedto refer to a human gene, normally inte-grated into chromosome 13, some alleles ofwhich cause susceptibility to breast andovarian cancer.

V. CONCLUSIONS OF LAW

A. The Summary Judgment Standard

Summary judgment is granted onlywhere there exists no genuine issue ofmaterial fact and the moving party is enti-tled to judgment as a matter of law. Fed.R.Civ.P. 56(c); see Celotex Corp. v. Catrett,477 U.S. 317, 322–23, 106 S.Ct. 2548, 91L.Ed.2d 265 (1986); SCS Commc’ns, Inc.v. Herrick Co., 360 F.3d 329, 338 (2d Cir.2004). The courts do not try issues of facton a motion for summary judgment, but,rather, determine ‘‘whether the evidencepresents a sufficient disagreement to re-quire submission to a jury or whether it isso one-sided that one party must prevail asa matter of law.’’ Anderson v. LibertyLobby, Inc., 477 U.S. 242, 251–52, 106 S.Ct.2505, 91 L.Ed.2d 202 (1986).

‘‘The party seeking summary judgmentbears the burden of establishing that nogenuine issue of material fact exists andthat the undisputed facts establish [its]right to judgment as a matter of law.’’Rodriguez v. City of New York, 72 F.3d1051, 1060–61 (2d Cir.1995). In determin-ing whether a genuine issue of materialfact exists, a court must resolve all ambi-guities and draw all reasonable inferencesagainst the moving party. See MatsushitaElec. Indus. Co. v. Zenith Radio Corp., 475U.S. 574, 587–88, 106 S.Ct. 1348, 89L.Ed.2d 538 (1986); Gibbs–Alfano v. Bur-ton, 281 F.3d 12, 18 (2d Cir.2002). Howev-er, ‘‘the non-moving party may not rely


simply on conclusory allegations or specu-lation to avoid summary judgment, butinstead must offer evidence to show thatits version of the events is not whollyfanciful.’’ Morris v. Lindau, 196 F.3d 102,109 (2d Cir.1999) (internal quotation marksomitted).

Summary judgment is appropriatewhere the moving party has shown that‘‘little or no evidence may be found insupport of the nonmoving party’s case.When no rational jury could find in favorof the nonmoving party because the evi-dence to support its case is so slight, thereis no genuine issue of material fact and agrant of summary judgment is proper.’’Gallo v. Prudential Residential Servs.,L.P., 22 F.3d 1219, 1223–24 (2d Cir.1994)(internal citations omitted).

B. 35 U.S.C. § 101 and Its Scope

Section 101 of Title 35, United StatesCode, provides:

Whoever invents or discovers any newand useful process, machine, manufac-ture, or composition of matter, or anynew and useful improvement thereof,may obtain a patent therefore, subject tothe conditions and requirements of thistitle.

In interpreting this language, the Su-preme Court has observed that ‘‘Congressplainly contemplated that the patent lawswould be given wide scope.’’ Diamond v.Chakrabarty, 447 U.S. 303, 308, 100 S.Ct.2204, 65 L.Ed.2d 144 (1980); see alsoJ.E.M. Ag Supply, Inc. v. Pioneer Hi–

Bred Int’l, Inc., 534 U.S. 124, 131, 122S.Ct. 593, 151 L.Ed.2d 508 (2001) (‘‘[W]eare mindful that this Court has alreadyspoken clearly concerning the broad scopeand applicability of § 101.’’).

[9] However, this broad reading of§ 101 and statutory patent eligibility is notwithout limits. ‘‘The Supreme Court hasrecognized that scientific principles andlaws of nature, even when for the firsttime discovered, have existed throughouttime, define the relationship of man to hisenvironment, and, as a consequence, oughtnot to be the subject of exclusive rights toany one person.’’ In re Meyer, 688 F.2d789, 795 (C.C.P.A.1982) (citing Le Roy v.Tatham, 55 U.S. (14 How.) 156, 175, 14L.Ed. 367 (1852)). Specifically, the Su-preme Court has recognized three catego-ries of subject-matter that fall outside thescope of § 101: ‘‘The laws of nature, phys-ical phenomena, and abstract ideas havebeen held not patentable.’’ Chakrabarty,447 U.S. at 309, 100 S.Ct. 2204; see alsoDiamond v. Diehr, 450 U.S. 175, 185, 101S.Ct. 1048, 67 L.Ed.2d 155 (1981). ‘‘Therule that the discovery of a law of naturecannot be patented rests, not on the notionthat natural phenomena are not processes,but rather on the more fundamental un-derstanding that they are not the kind of‘discovery’ that the statute was enacted toprotect.’’ Parker v. Flook, 437 U.S. 584,593, 98 S.Ct. 2522, 57 L.Ed.2d 451 (1978).

The exclusion of products of nature 40 aspatentable subject matter under § 101 also

40. Myriad distinguishes between ‘‘laws of na-ture,’’ ‘‘natural phenomena,’’ and ‘‘abstractideas,’’ which it concedes are not patentable,and ‘‘products of nature,’’ for which it ap-pears to argue no prohibition to patentabilityexists. Although the distinction betweenthese two categories is unclear, it is wellestablished that ‘‘products of nature’’ are notpatentable. See, e.g., Chakrabarty, 447 U.S. at313, 100 S.Ct. 2204 (stating that relevant dis-

tinction for § 101 patentability is ‘‘betweenproducts of nature, whether living or not, andhuman-made inventions’’); Gen. Elec. Co. v.De Forest Radio Co., 28 F.2d 641, 642 (3dCir.1928) (noting that ‘‘a patent cannot beawarded for a discovery or for a product ofnature, or for a chemical element’’); In reMarden, 18 C.C.P.A. 1046, 47 F.2d 957, 957(1931) (concluding that ‘‘[u]ranium is a prod-uct of nature, and the appellant is not entitled


reflects the Supreme Court’s recognitionthat ‘‘[p]henomena of nature, though justdiscovered, mental processes, and abstractintellectual concepts are not patentable, asthey are the basic tools of scientific andtechnological work.’’ Gottschalk v. Ben-son, 409 U.S. 63, 67, 93 S.Ct. 253, 34L.Ed.2d 273 (1972). Thus, as JusticeBreyer has observed, ‘‘the reason for thisexclusion is that sometimes too much pat-ent protection can impede rather than‘promote the Progress of Science and use-ful Arts,’ the constitutional objective ofpatent and copyright protection.’’ Lab.Corp. of Am. Holdings v. Metabolite Labs.,Inc., 548 U.S. 124, 126–27, 126 S.Ct. 2921,165 L.Ed.2d 399 (2006) (Breyer, J., dis-senting) (quoting U.S. Const., Art. I, § 8,cl. 8.) (emphasis in original). For thesereasons, ‘‘manifestations of laws of nature[are] free to all men and reserved exclu-sively to none.’’ Funk Bros. Seed Co. v.Kalo Inoculant Co., 333 U.S. 127, 130, 68S.Ct. 440, 92 L.Ed. 588 (1948).

[10] The inquiry into an invention’spatent eligibility is a fundamental one, andas such, ‘‘[t]he obligation to determinewhat type of discovery is sought to bepatented must precede the determinationof whether that discovery is, in fact, newor obvious.’’ Flook, 437 U.S. at 593, 98S.Ct. 2522; see also In re Bilski, 545 F.3d943, 950 (Fed.Cir.2008) (en banc), cert.granted, ––– U.S. ––––, 129 S.Ct. 2735, 174L.Ed.2d 246 (2009) (‘‘Whether a claim isdrawn to patent-eligible subject matter un-der § 101 is a threshold inquiry, and anyclaim of an application failing the require-ments of § 101 must be rejected even if itmeets all of the other legal requirementsof patentability.’’) (citing In re Comiskey,499 F.3d 1365, 1372 (Fed.Cir.2007)); Pro-

metheus Labs. v. Mayo CollaborativeServs., 581 F.3d 1336, 1343 (Fed.Cir.2009)(noting that in determining patent eligibili-ty, ‘‘it is improper to consider whether aclaimed element or step in a process isnovel or nonobvious, since such consider-ations are separate requirements set forthin 35 U.S.C. §§ 102 and 103, respectively.’’(citing Bilski, 545 F.3d at 958)). Consis-tent with this approach, the courts haverejected patent claims even when the pur-ported invention was highly beneficial ornovel, or the research and work that wentinto identifying it was costly or time-con-suming. See, e.g., Funk Bros., 333 U.S. at130, 68 S.Ct. 440; Am. Fruit Growers, Inc.v. Brogdex Co., 283 U.S. 1, 11–13, 51 S.Ct.328, 75 L.Ed. 801 (1931); Gen. Elec. Co. v.De Forest Radio Co., 28 F.2d 641, 642–43(3d Cir.1928).

The distinction between the § 101 inqui-ry into patentable subject matter and theother requirements for patentability setforth in Title 35 is of particular importancein evaluating the authorities cited by theparties and the arguments presented.The discussion of § 101 in In re Bergy, 596F.2d 952 (C.C.P.A.1979) by the late Honor-able Giles S. Rich, one of the authors ofthe 1952 Patent Act, is particularly infor-mative in clarifying the proper scope of a§ 101 analysis. There, Judge Rich statedwhat considerations were salient—and im-portantly, what considerations were not—in a § 101 analysis:

Section 101 states three requirements:novelty, utility, and statutory subjectmatter. The understanding that thesethree requirements are separate anddistinct is long-standing and has beenuniversally acceptedTTTT Thus, the ques-tions of whether a particular invention is

to a patent on the same, or upon any of theinherent natural qualities of that metal’’); Inre Marden, 18 C.C.P.A. 1057, 47 F.2d 958, 959(1931) (stating that ‘‘pure vanadium is not

new in the inventive sense, and, it being aproduct of nature, no one is entitled to amonopoly of the same’’).


novel or useful are questions whollyapart from whether the invention fallsinto a category of statutory subject mat-ter. Of the three requirements stated in§ 101, only two, utility and statutorysubject matter, are applied under § 101.As we shall show, in 1952 Congressvoiced its intent to consider the noveltyof an invention under § 102 where it isfirst made clear what the statute meansby ‘‘new,’’ notwithstanding the fact thatthis requirement is first named in § 101.

Id. at 960–61 (emphasis added). JudgeRich further cautioned that ‘‘statements inthe older cases must be handled with carelest the terms used in their reasoningclash with the reformed terminology of thepresent statute; lack of meticulous caremay lead to distorted legal conclusions.’’Id. at 959. The Supreme Court subse-quently affirmed this understanding of the§ 101 analysis in Diehr, noting that whileit had been argued that ‘‘novelty is anappropriate consideration under § 101,’’‘‘[t]he question TTT of whether a particularinvention is novel is ‘wholly apart fromwhether from whether the invention fallsinto a category of statutory subject mat-ter.’ ’’ 450 U.S. at 189–90, 101 S.Ct. 1048(quoting Bergy, 596 F.2d at 961); see alsoBilski, 545 F.3d at 958 (‘‘So here, it isirrelevant to the § 101 analysis whetherApplicants’ claimed process is novel ornon-obvious.’’).

Accordingly, in considering whether thepatents-in-suit comply with § 101, theproper analysis requires determining (1)whether the claimed invention possessesutility; and (2) whether the claimed inven-tion constitutes statutory subject matter,that is, whether it is a ‘‘process, machine,manufacture, or composition of matter, orany new and useful improvement thereof,’’35 U.S.C. § 101, or whether the claimedinvention instead falls within the judiciallycreated ‘‘products of nature’’ exception topatentable subject matter, i.e., ‘‘laws of

nature, natural phenomenon, and abstractideas,’’ Chakrabarty, 447 U.S. at 309, 100S.Ct. 2204. In contrast, the question ofwhether an invention is ‘‘new’’ or ‘‘novel’’over the prior art is a question addressedby § 102 and falls outside of the scope ofthe present § 101 analysis. Because it isundisputed that the claimed compositionsand methods possess utility, the sole taskof this Court is to resolve whether theclaimed compositions and methods consti-tute statutory subject matter or fall withinthe judicially created products of natureexception to patentable subject matter.

C. The Composition Claims Are In-valid Under 35 U.S.C. § 101

As noted, the issue presented by theinstant motions with respect to the compo-sition claims is whether or not claims di-rected to isolated DNA containing natural-ly-occurring sequences fall within theproducts of nature exception to § 101.Based upon the reasons set forth below, itis concluded that the composition claims-in-suit are excepted.

1. Consideration of the meritsof Plaintiffs’ challenge is

appropriate.

Myriad offers several arguments forwhy this Court should not engage the sub-stance of Plaintiffs’ claims, but should in-stead dismiss them out of hand. Foremostamong them is Myriad’s assertion thatPlaintiffs’ claims should be dismissed inlight of the ‘‘carefully considered policy ofthe USPTO,’’ which is ‘‘entitled to greatrespect from the courts.’’ Myriad Br. at26. In so arguing, Myriad notes the pre-sumption of validity afforded to patents,see 35 U.S.C. § 282, and the USPTO’sprior consideration of the eligibility ofgene-related patents, see Utility Examina-tion Guidelines 66 Fed. Reg. 1092, 1092–99(Jan. 5, 2001), as well as the Supreme


Court’s statements in J.E.M. Ag Supply,534 U.S. 124, 122 S.Ct. 593.

The Federal Circuit has previously heldthat it owes no deference to USPTO legaldeterminations. See, e.g., Arnold P’shipv. Dudas, 362 F.3d 1338, 1340 (Fed.Cir.2004) (‘‘This court reviews statutory inter-pretation, the central issue in this case,without deference.’’). While Congress hascreated a presumption of validity for is-sued patents, approximately 40% of pat-ents challenged in the courts have beenfound invalid, demonstrating that this pre-sumption is far from absolute. See Insti-tute for Intellectual Property & Informa-tion Law, University of Houston LawCenter, Patstats.org, Full Calendar Year2008 Report, http://www.patstats.org/2008 Full Year Posting.rev3.htm (indicat-ing that 40% of all validity determinationsin federal court in 2008 found the chal-lenged patent invalid); Paul F. Morgan &Bruce Stoner, Reexamination v. Litiga-tion—Making Intelligent Decisions inChallenging Patent Validity, 86 J. Pat. &Trademark Off. Soc’y 441–461 (2004) (cit-ing USPTO statistics showing that 74% ofpatents previously issued by the PatentOffice and later challenged through thereexamination process were either can-celed or changed by the USPTO). More-over, the lack of Congressional action tospecifically prohibit gene patents in re-sponse to the USPTO’s prior grant ofsuch patents does not preclude their re-view by the courts. For example, in Bil-ski, 545 F.3d 943, the Federal Circuit setout a test for the patentability of methodclaims that potentially will invalidate thou-sands of patents on business method pat-ents, despite Congress’ silence concerningthe patentability of such methods. Final-ly, while the Supreme Court in J.E.M. AgSupply noted the USPTO’s practice of is-suing patents on sexually reproducingplants in concluding that such plants rep-resented patentable subject matter under

§ 101, that passing observation was nei-ther dispositive nor central to the Court’sholding and does not establish a rule ofjudicial deference to the USPTO’s prac-tices. See J.E.M. Ag Supply, 534 U.S. at144–45, 122 S.Ct. 593. Indeed, the judi-cial deference urged by Myriad is difficultto reconcile with the courts’ considerationof the substantive issues presented incases such as Chakrabarty and indeed,J.E.M. Ag Supply itself.

Moreover, in the absence of a § 101challenge to patent validity, the fact thatcourts have previously upheld the validityof patents directed to biological productsin response to § 102 and/or § 103 chal-lenges has no bearing on the present in-quiry. See, e.g., In re Kubin, 561 F.3d1351 (Fed.Cir.2009) (considering obvious-ness of claims); In re O’Farrell, 853 F.2d894 (Fed.Cir.1988) (same). The PatentAct sets out patent invalidity as an issue tobe raised by the parties, see 35 U.S.C.§ 282, and it would be erroneous to treat acase involving DNA-related patents asholding that isolated human genes consti-tute patentable subject matter under§ 101. Were that the case, the SupremeCourt could have proceeded with its con-sideration of Metabolite Labs., after itgranted certiorari and the parties and ami-ci had fully briefed the issue of patentablesubject matter eligibility, rather than dis-missing certiorari as improvidently grant-ed based on the parties’ failure to raise the§ 101 issue below. 548 U.S. 124, 126 S.Ct.2921.

Finally, Myriad’s suggestion that invali-dating the patents-in-suit would constitutean unconstitutional taking in violation ofthe Fifth Amendment of the Constitutionor a violation of the United States’ obli-gations under the Agreement on Trade–Related Aspects of Intellectual PropertyRights (‘‘TRIPS’’) is unpersuasive. Myri-ad’s novel takings argument runs counter


to a long history of invalidation of patentclaims by the courts and is unsupported bylegal precedent. Similarly, Articles 8.1and 27.3 of TRIPS permit governments toincorporate public health concerns intotheir intellectual property laws and to ex-clude from patentability diagnostic, thera-peutic, or surgical methods as well as par-ticular inventions on the grounds of publicinterest. As a result, invalidation of thepatents-in-suit would constitute neither aconstitutional violation nor a conflict withthe United States’ treaty obligations.

2. Patentable subject matter mustbe ‘‘markedly different’’ from

a product of nature

Supreme Court precedent has estab-lished that products of nature do not con-stitute patentable subject matter absent achange that results in the creation of afundamentally new product. In AmericanFruit Growers, the Supreme Court reject-ed patent claims covering fruit whose skinhad been treated with mold-resistant bo-rax. Acknowledging that the ‘‘complete ar-ticle is not found in nature,’’ and ‘‘treat-ment, labor and manipulation’’ went intoproducing the fruit, the Court nonethelessheld that the fruit did not become an ‘‘arti-cle of manufacture’’ unless it ‘‘possesses anew or distinctive form, quality, or proper-ty’’ compared to the naturally-occurring

article.41 283 U.S. at 11, 51 S.Ct. 328.The Court went on to observe:

Manufacture implies a change, but everychange is not manufacture, and yet ev-ery change in an article is the result oftreatment, labor, and manipulation. Butsomething more is necessary TTTT Theremust be transformation; a new and dif-ferent article must emerge having a dis-tinctive name, character, or use.

Id. at 12–13, 51 S.Ct. 328 (quoting Anheu-ser–Busch Brewing Ass’n v. United States,207 U.S. 556, 562, 28 S.Ct. 204, 52 L.Ed.336 (1908)) (internal citation and quotationmarks omitted).

Similarly, in Funk Brothers, the Su-preme Court considered whether a mix-ture of several naturally-occurring speciesof bacteria was patentable.42 333 U.S. at128–31, 68 S.Ct. 440. Each species ofbacteria in the mixture could extract nitro-gen from the air for plant usage. Whilethe patent holder had created a mixture byselecting and testing for strains of bacteriathat did not mutually inhibit one another,the Court concluded that the patent holder‘‘did not create a state of inhibition or ofnon-inhibition in the bacteria. Their quali-ties are the work of nature. Those quali-ties are of course not patentable.’’ Id. at130, 68 S.Ct. 440.

Most recently, the Supreme Court ad-dressed the application of § 101 to prod-

41. Myriad argues that American Fruit Grow-ers was decided on novelty grounds, ratherthan subject matter patentability. See MyriadBr. at 26. However, the Court’s novelty dis-cussion was restricted to its analysis of theprocess claims. Am. Fruit Growers, 283 U.S.at 13–14, 51 S.Ct. 328 (‘‘If it be assumed thatthe process claims under consideration coveran invention, we think this lacked noveltywhen application was made for the patentAugust 13, 1923’’). In contrast, its rejectionof the composition claims was based on ananalysis of subject matter patentability. Seeid. at 11, 51 S.Ct. 328 (‘‘Is an orange, the rindof which has become impregnated with bo-rax, through immersion in a solution, and

thereby resistant to blue mold decay, a ‘manu-facture,’ or manufactured article, within themeaning of section 31, title 35, U.S.Code?’’).

42. Myriad suggests that the Supreme Court’sholding in Funk Brothers was premised on anobviousness determination, rather than pat-entable subject matter. Subsequent SupremeCourt opinions, however, have treated theholding in Funk Brothers as a statement ofpatentable subject matter. See Chakrabarty,447 U.S. at 309–10, 100 S.Ct. 2204; Flook,437 U.S. at 591–92, 98 S.Ct. 2522; Benson,409 U.S. at 67–68, 93 S.Ct. 253.


uct claims in Diamond v. Chakrabarty,447 U.S. 303, 100 S.Ct. 2204, 65 L.Ed.2d144. In Chakrabarty, the Court consid-ered whether a ‘‘live, human-made micro-organism is patentable subject matter un-der 35 U.S.C. § 101.’’ Id. at 305, 100S.Ct. 2204. The microorganism in ques-tion was a bacterium that had been genet-ically engineered to break down multiplecomponents of crude oil and possessedconsiderable utility in the treatment of oilspills. Id. In concluding that the man-made bacterial strain was patentable, theCourt observed that the claim ‘‘is 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.’ ’’ Id. at 309–10, 100 S.Ct. 2204 (quoting Hartranft v.Wiegmann, 121 U.S. 609, 615, 7 S.Ct.1240, 30 L.Ed. 1012 (1887)). The Courtwent on to contrast the Chakrabarty bac-terium with the bacterial mixture at issuein Funk Brothers, stating that in Chakra-barty’s case, ‘‘the patentee has produced anew bacterium with markedly differentcharacteristics from any found in natureand one having the potential for signifi-cant utility. His discovery is not nature’shandiwork, but his ownTTTT’’ Id. at 310,100 S.Ct. 2204.43 This requirement thatan invention possess ‘‘markedly differentcharacteristics’’ for purposes of § 101 re-flects the oft-repeated requirement that aninvention have ‘‘a new or distinctive form,quality, or property’’ from a product ofnature. Am. Fruit Growers, 283 U.S. at

11, 51 S.Ct. 328; In re Merz, 25 C.C.P.A.1314, 97 F.2d 599, 601 (1938) (‘‘[M]erepurification of known materials does notresult in a patentable product,’’ unless‘‘the product obtained in such a case hadproperties and characteristics which weredifferent in kind from those of the knownproduct rather than in degree.’’).

Courts have also specifically held that‘‘purification’’ of a natural compound,without more, is insufficient to render aproduct of nature patentable. In TheAmerican Wood–Paper Co. v. The FibreDisintegrating Co., 90 U.S. (23 Wall.) 566,23 L.Ed. 31 (1874), the Supreme Courtheld that refined cellulose, consisting ofpurified pulp derived from wood and vege-table, was unpatentable because it was‘‘an extract obtained by the decompositionor disintegration of material substance.’’Id. at 593. As the Court observed:

There are many things well known andvaluable in medicine or in the arts whichmay be extracted from divers[e] sub-stances. But the extract is the same, nomatter from what it has been taken. Aprocess to obtain it from a subject fromwhich it has never been taken may bethe creature of invention, but the thingitself when obtained cannot be called anew manufacture.

Id. at 593–94.44 Similarly, in Cochrane v.Badische Anilin & Soda Fabrik, 111 U.S.293, 4 S.Ct. 455, 28 L.Ed. 433 (1884), theCourt rejected a patent on an artificialversion of a natural red dye called aliza-rine that was produced by manipulating

43. Although Chakrabarty is often cited for theproposition that ‘‘anything under the sun thatis made by man’’ is patentable, id. at 309, 100S.Ct. 2204, that phrase is a misleading quota-tion from the legislative history of the PatentAct of 1952. The full quote clearly acknowl-edges the statutory limitations to patentablesubject matter: ‘‘A person may have ‘invent-ed’ a machine or a manufacture, which mayinclude anything under the sun made by man,

but it is not necessarily patentable under sec-tion 101 unless the conditions of the title arefulfilled.’’ H.R.Rep. No.1923, 82d Cong., 2dSess. 6 (1952).

44. Given the posture of the challenge to thepatent’s validity, the Court rested its holdingon the fact that the patent in question wasinvalid as non-novel. Id.


another compound through acid, heat, wa-ter or distillation. See generally, id. Al-though the artificial version of the dye wasof a brighter hue than the naturally occur-ring dye, the Court concluded that ‘‘[c]ail-ing it artificial alizarine did not make it anew composition of matter, and patentableas suchTTTT’’ Id. at 311, 4 S.Ct. 455 (citingAm. Wood–Paper, 90 U.S. (23 Wall.) at593).

In General Electric, 28 F.2d at 642, theThird Circuit Court of Appeals consideredthe patentability of purified tungsten,which possessed superior characteristicsand utility over its brittle, naturally-occur-ring form. The court first noted that ‘‘[i]fit is a natural thing then clearly, even if[the patentee] was the first to uncover itand bring it into view, he cannot have apatent for it because a patent cannot beawarded for a discovery or for a product ofnature, or for a chemical element.’’ Id.The court went on to state:

Naturally we inquire who created puretungsten. Coolidge? No. It existed innature and doubtless has existed therefor centuries. The fact that no one be-fore Coolidge found it there does notnegative its origin or existence.The second part of the claim reads:‘‘Having ductility and high tensilestrength.’’ Did Coolidge give thosequalities to ‘‘substantially pure tung-sten’’? We think not for it is now con-ceded that tungsten pure is ductile cold.If it possess that quality now it is certainthat it possessed it always.

Id. at 643. The Court of Customs andPatent Appeals (‘‘C.C.P.A.’’), the precursorto the Federal Circuit Court of Appeals,45

subsequently relied on General Electric inrejecting patents claiming purified urani-um and vanadium. See In re Marden, 18C.C.P.A. 1046, 47 F.2d 957, 957–58 (1931)(‘‘Marden I ’’); In re Marden, 18 C.C.P.A.1057, 47 F.2d 958, 959 (1931) (‘‘MardenII ’’) (‘‘The quality of purity of vanadium orits ductility is a quality of a natural prod-uct and as such is not patentable.’’). Simi-larly, in Ex Parte Latimer, the PatentCommissioner refused to allow a patent onpine needle fibers that were better suitedfor textile production, even though it wasnecessary to remove the needle from itssheath and other resinous material. 1889Dec. Comm’r Pat. 123, 125 (1889) (‘‘Naturemade them so and not the process bywhich they are taken from the leaf orneedle.’’).

Myriad argues that purification of ‘‘ ‘nat-urally occurring’ compounds that ‘do notexist in nature in pure form’ renders suchcompounds patent-eligible.’’ Myriad Br. at21 (quoting In re Bergstrom, 57 C.C.P.A.1240, 427 F.2d 1394, 1401 (1970)). Howev-er, Myriad cites no Supreme Court author-ity that would rebut the authorities pre-sented by Plaintiffs, nor do the cited casessupport Myriad’s position.

Myriad has relied heavily on the holdingof the Honorable Learned Hand in Parke–Davis & Co. v. H.K. Mulford Co., 189 F.95 (S.D.N.Y.1911).46 In Parke–Davis,

45. The decisions of the C.C.P.A. remain bind-ing precedent in patent cases. See SouthCorp. v. United States, 690 F.2d 1368, 1370–71(Fed.Cir.1982) (en banc) (adopting ‘‘[t]hatbody of law represented by the holdings of TTT

the Court of Customs and Patent Appeals’’ as‘‘precedent’’ for the then-new Federal Circuitso as to ‘‘continu[e] the stability in those areasof the law previously within the jurisdiction ofour predecessor courts’’).

46. The invocation of Judge Hand is frequent-ly practiced in this Circuit. See, e.g., UnitedStates v. Rigas, 583 F.3d 108, 121 n. 3 (2dCir.2009) (quoting Learned Hand for theproposition that appellate courts may not findfacts); United States v. Parker, 554 F.3d 230(2d Cir.2009) (quoting Learned Hand for hisformulation of the requirements of conspira-cy); In re City of New York, 522 F.3d 279,284 (2d Cir.2008) (citing Learned Hand forhis formulation of negligence); In re Hyman,


Judge Hand considered a challenge to thevalidity of a patent claiming an adrenalinecompound that had been isolated and puri-fied from animal suprarenal glands. Id. at97. It had been known that suprarenalglands in powdered form had hemostatic,blood-pressure-raising and astringentproperties, but could not be used for thosepurposes in gross form. The isolatedadrenaline, however, possessed the desiredtherapeutic properties and could be admin-istered to humans.

Although Myriad argues that the hold-ing in Parke–Davis establishes that thepurification of a natural product necessari-ly renders it patentable, the opinion, readclosely, fails to support such a conclusion.The question before the court in Parke–Davis was one of novelty (a modern-day§ 102 question), not of patentable subjectmatter (the § 101 question before thisCourt). In framing the issue, Judge Handobserved that, ‘‘[the validity of the claims]is attacked, first, because they are antici-pated in the art; and second, for a numberof technical grounds which I shall take upin turn.’’ Id. at 101 (emphasis added). He

went on to conclude that the patentedpurified extract was not, in fact, differentfrom the prior art ‘‘only for a degree ofpurity,’’ but rather was a different chemi-cal substance from that found in the priorart. Id. at 103 (observing that ‘‘no one hadever isolated a substance [adrenaline]which was not in salt form’’ and that ‘‘the[claimed] base [form of adrenaline] was anoriginal production of [the patentee’s]’’).Thus, Judge Hand held that the purifiedadrenaline was not anticipated by the priorart, namely, the ground paradrenal glandthat was known to possess certain benefi-cial properties. See Merck & Co. v. OlinMathieson Chem. Corp., 253 F.2d 156, 162(4th Cir.1958) (‘‘It was further held [inParke–Davis ] that the invention was notanticipated, though the principle wasknown to exist in the suprarenal glands.’’).

Only after concluding that the claimedpurified adrenaline was novel over the pri-or art did Judge Hand offer, as dicta, thestatement to which Myriad cites: ‘‘But,even if it were merely an extracted prod-uct without change, there is no rule thatsuch products are not patentable.’’ Id. at

man, 502 F.3d 61, 67 (2d Cir.2007) (quotingat length Learned Hand’s inconclusive dis-cussion of the meaning of the word ‘‘defalca-tion’’ in 11 U.S.C. § 523(a)(4)); United Statesv. Brand, 467 F.3d 179, 190 (2d Cir.2006)(quoting Learned Hand’s definition of in-ducement by the government); In re EnronCorp., 419 F.3d 115, 123 (2d Cir.2005) (quot-ing Learned Hand’s critique of statutes oflimitations); Shannon v. Jacobowitz, 394F.3d 90, 95 (2d Cir.2005) (quoting LearnedHand’s instruction that ‘‘[w]ords are not peb-bles in alien juxtaposition TTTT’’); Danahy v.Buscaglia, 134 F.3d 1185, 1189 (2d Cir.1998)(quoting Learned Hand on the rationale forqualified immunity). See also, Remarks of theHonorable John M. Wallcer, Jr. Upon Receiv-ing the Learned Hand Medal for Excellence inFederal Jurisprudence, 76 St. John’s L.Rev.595, 596 (2002) (‘‘Judge Hand is widely con-sidered to have been one of the four greatestjudges of the first half of the twentieth centu-ry.’’); James L. Oakes, Personal Reflections

on Learned Hand and the Second Circuit, 47Stan. L.Rev. 387 (1995); Gerald Gunther,Learned Hand: the Man and the Judge (1994);Kathryn Griffin, Judge Learned Hand and theRole of the Federal Judiciary (1973); MarvinSchick, Learned Hand’s Court (1970); MarciaNelson, ed., The Remarkable Hands: An Af-fectionate Portrait (1983); Hershel Shanks,ed., The Art and Craft of Judging: The Deci-sions of Judge Learned Hand (1968). Al-though Judge Hand once turned his back onthe author of this opinion arguing before himon behalf of the Government, his opinion inParke–Davis deserves careful review butbrings to mind that oft repeated adage‘‘Quote Learned, but follow Gus.’’ See Oakes,47 Stan. L.Rev. at 389 n. 175. This author,confronted by genomics and molecular biolo-gy, also emphatically empathizes with JudgeHand’s complaint in Parke–Davis about hislack of knowledge of the rudiments of chem-istry. See Parke–Davis, 189 F. at 114.


103. While the accuracy of this statementat the time was written is dubious in lightof American Wood–Paper (to which JudgeHand did not cite) it is certainly no longergood law in light of subsequent SupremeCourt cases, which, as noted above, re-quire that a claimed invention possess‘‘markedly different characteristics’’ overproducts existing in nature in order for itto constitute patentable subject matter.47

Chakrabarty, 447 U.S. at 310, 100 S.Ct.2204; see also Funk Bros., 333 U.S. at130–32, 68 S.Ct. 440. By the same token,Judge Hand’s suggestion that a claimedinvention was patentable since it was a‘‘new thing commercially and therapeuti-cally,’’ Parke–Davis, 189 F. at 103, is firm-ly contradicted by subsequent case lawestablishing that ‘‘it is improper to consid-er whether a claimed element or step in aprocess is novel or nonobvious, since suchconsiderations are separate requirements’’when evaluating whether a claim is patent-eligible subject matter. Prometheus, 581F.3d at 1343; see also Bergy, 596 F.2d at960–61. Such an approach would also beinconsistent with the Supreme Court’s re-jection of the patentability of the commer-cially useful mixture of bacteria in FunkBrothers, the refined cellulose in Ameri-can Wood–Paper, and the electromagneticcommunication devices in O’Reilly v.Morse, 56 U.S. (15 How.) 62, 14 L.Ed. 601(1853).

The distinction between considerationsof novelty and patentable subject mattersimilarly undermines Myriad’s reliance onBergstrom and In re Kratz, 592 F.2d 1169(C.C.P.A.1979), both of which presentedissues of novelty and anticipation ratherthan the question of patentable subjectmatter. In Bergstrom, the C.C.P.A. con-sidered an appeal from a rejection by the

Board of Patent and Interferences(‘‘BPAI’’) of a patent claiming the purifiedprostaglandins PGE2 and PGE3 that hadbeen extracted from human or animalprostate glands. 427 F.2d at 1398. Al-though the BPAI cited § 101 in its rejec-tion, the C.C.P.A. recognized the issue as a§ 102 question of novelty. Id. at 1400(‘‘Tested by the conventional evidentiarycriteria or ‘conditions for patentability’ rel-evant to the present factual situation whichCongress has expressed in the various pro-visions of 35 U.S.C. § 102, appellants areundoubtedly correct, for the Patent Officehas not been able to TTT establish that theclaimed subject matter lacks ‘novelty.’ ’’);see also id. at 1401 (‘‘[T]he fundamentalerror in the board’s position, as we see it,is the analysis and answer it gave to thesole issue it accurately posed—whether theclaimed pure materials are novel as com-pared with the less pure materials of thereference.’’ (internal citation and quotationmarks omitted)). Indeed, the C.C.P.A. it-self has subsequently recognized thatBergstrom is properly viewed as a caseconcerning novelty. Bergy, 596 F.2d at961 (‘‘Our research has disclosed only twoinstances in which rejections for lack ofnovelty were made by the PTO under§ 101 TTTT In In re Bergstrom we in effecttreated the rejection as if it had beenmade under § 102, observing in the pro-cess that ‘The word ‘‘new’’ in § 101 isdefined and to be construed in accordancewith the provisions of § 102.’ ’’ (internalcitation omitted)).

Kratz examined the rejection of a patentclaiming a substantially purified chemicalcompound naturally occurring in strawber-ries, called 2–methyl–2–pentenoic acid(‘‘2M2PA’’). 592 F.2d at 1170. The paten-tee had appealed from the BPAI’s deter-

47. Notwithstanding Judge Hand’s reputation,see supra note 46, his opinion in Parke–Daviswas one of a district court judge and does not

supersede contrary statements of the law bythe C.C.P.A. or the Supreme Court.


mination that the purified compound wasobvious over the prior art under § 103.See id. Although there was some discus-sion about whether the compositionclaimed was a naturally-occurring com-pound, the C.C.P.A. did not view the ques-tion before it as a § 101 inquiry. Instead,the court treated the appeal as a questionof novelty and anticipation pursuant to§ 102.48 See, e.g., id. at 1174 (‘‘It shouldbe clear that an anticipation rejection insuch a case is necessarily based on a dualfooting.’’).49

Finally, Merck & Co., Inc. v. Olin Ma-thieson Chem. Corp., 253 F.2d 156, citedby Myriad, is entirely consistent with theprinciple set forth in Funk Brothers andAmerican Fruit Growers that somethingderived from a product of nature must‘‘possess a new or distinctive form, quality,or property’’ in order to become patentablesubject matter. Am. Fruit Growers, 283U.S. at 11, 51 S.Ct. 328. In Merck, theFourth Circuit considered the validity of apatent claiming a Vitamin B12 compositionuseful for treating pernicious anemia. Id.at 157. Although naturally occurring Vita-min B12 produced in cows had known ther-apeutic properties and was commerciallyavailable, the court found the purified B12composition, which was obtained from amicroorganism, patentable. In upholdingthe validity of the patent, the court held:

Every slight step in purification does notproduce a new product. What is gainedmay be the old product, but with agreater degree of purity. Alpha alumi-na purified is still alpha alumina, In reRidgway, [22 C.C.P.A. 1169] 76 F.2d602, and ultramarine from which floata-ble impurities have been removed is stillultramarine, In re Merz, [25 C.C.P.A.1314] 97 F.2d 599 TTT

Id. at 163. Because the court concludedthat the purified B12 was more than a‘‘mere advance in the degree of purity of aknown product,’’ it determined that theclaimed invention was entitled to patentprotection. Id. at 164.

In sum, the clear line of Supreme Courtprecedent and accompanying lower courtauthorities, stretching from AmericanWood–Paper through to Chakrabarty, es-tablishes that purification of a product ofnature, without more, cannot transform itinto patentable subject matter. Rather,the purified product must possess ‘‘mark-edly different characteristics’’ in order tosatisfy the requirements of § 101.

3. The claimed isolated DNA isnot ‘‘markedly different’’

from native DNA.

[11] The question thus presented byPlaintiffs’ challenge to the compositionclaims is whether the isolated DNAclaimed by Myriad possesses ‘‘markedlydifferent characteristics’’ from a product of

48. The differences between the test applied inKratz and the ‘‘markedly different’’ require-ment set forth in Chakrabarty and other Su-preme Court precedent further demonstratesthat the Kratz court was engaged in a § 102anticipation analysis and not a § 101 statuto-ry subject matter analysis. See id. at 1174(requiring, for a finding of anticipation, that‘‘the natural composition must inherentlycontain the naturally occurring compound’’and that ‘‘the claim must be of sufficientbreadth to encompass both the known naturalcomposition and the naturally occurring com-pound.’’).

49. Bergy, also cited by Myriad, considered thequestion of whether microorganisms consti-tuted patentable subject matter, an issue sub-sequently addressed by the Supreme Court inChakrabarty. It did not address the patenta-bility of purified natural products, and itscitation to Merck and Parke–Davis was onlyfor the purpose of noting that courts hadupheld patents on pharmaceutical compoundssuch as vitamin B12 and adrenaline. SeeBergy, 596 F.2d at 974–75 & n. 13.


nature.50 Chakrabarty, 447 U.S. at 310,100 S.Ct. 2204. In support of its position,Myriad cites several differences betweenthe isolated DNA claimed in the patentsand the native DNA found within humancells. None, however, establish the sub-ject matter patentability of isolatedBRCA1/2 DNA.

The central premise of Myriad’s argu-ment that the claimed DNA is ‘‘markedlydifferent’’ from DNA found in nature isthe assertion that ‘‘[i]solated DNA mole-cules should be treated no differently thanother chemical compounds for patent eligi-bility,’’ Myriad Br. at 26, and that thealleged ‘‘difference in the structural andfunctional properties of isolated DNA’’render the claimed DNA patentable sub-ject matter, Myriad Br. at 31.

Myriad’s focus on the chemical nature ofDNA, however, fails to acknowledge theunique characteristics of DNA that differ-entiate it from other chemical compounds.As Myriad’s expert Dr. Joseph Straus ob-served: ‘‘Genes are of double nature: Onthe one hand, they are chemical substancesor molecules. On the other hand, they arephysical carriers of information, i.e., wherethe actual biological function of this infor-mation is coding for proteins. Thus, inher-ently genes are multifunctional.’’ StrausDecl. ¶ 20; see also The Cell at 98, 104(‘‘Today the idea that DNA carries geneticinformation in its long chain of nucleotidesis so fundamental to biological thoughtthat it is sometimes difficult to realize the

enormous intellectual gap that it filledTTTT

DNA is relatively inert chemically.’’); Kev-in Davies & Michael White, Breakthrough:The Race to Find the Breast Cancer Gene166 (1996) (noting that Myriad Genetics’April 1994 press release described itself asa ‘‘genetic information business’’). Thisinformational quality is unique among thechemical compounds found in our bodies,and it would be erroneous to view DNA as‘‘no different[ ]’’ than other chemicals pre-viously the subject of patents.51

Myriad’s argument that all chemicalcompounds, such as the adrenaline at issuein Parke–Davis, necessarily conveys someinformation ignores the biological realitiesof DNA in comparison to other chemicalcompounds in the body. The informationencoded in DNA is not information aboutits own molecular structure incidental toits biological function, as is the case withadrenaline or other chemicals found in thebody. Rather, the information encoded byDNA reflects its primary biological func-tion: directing the synthesis of other mole-cules in the body—namely, proteins, ‘‘bio-logical molecules of enormous importance’’which ‘‘catalyze biochemical reactions’’ andconstitute the ‘‘major structural materialsof the animal body.’’ O’Farrell, 853 F.2dat 895–96. DNA, and in particular theordering of its nucleotides, thereforeserves as the physical embodiment of lawsof nature—those that define the construc-tion of the human body. Any ‘‘informa-tion’’ that may be embodied by adrenaline

50. The parties do not appear to dispute thatisolated DNA claimed in the patents-in-suitare ‘‘useful’’ for purposes of § 101.

51. Myriad and many of the amici suggest thatthe invalidation of the patents-in-suit will re-sult in the decimation of the biotechnologyindustry. See, e.g., Myriad Br. at 28–29 (sug-gesting that a finding that DNA is unpatent-able subject matter will invalidate patents toimportant chemical compounds such as theanticancer drug Taxol (paclitaxel) and leave

‘‘little to nothing’’ of the United States bio-technology industry). The conclusionsreached in this opinion concerning the sub-ject matter patentability of isolated DNA,however, are based on the unique propertiesof DNA that distinguish it from all otherchemicals and biological molecules found innature. As a result. Myriad’s predictions forthe future of the U.S. biotechnology industryare unfounded.


and similar molecules serves no compara-ble function, and none of the declarationssubmitted by Myriad support such a con-clusion. Consequently, the use of simpleanalogies comparing DNA with chemicalcompounds previously the subject of pat-ents cannot replace consideration of thedistinctive characteristics of DNA.

In light of DNA’s unique qualities as aphysical embodiment of information, noneof the structural and functional differencescited by Myriad between native BRCA1/2DNA and the isolated BRCA1/2 DNAclaimed in the patents-in-suit render theclaimed DNA ‘‘markedly different.’’ Thisconclusion is driven by the overriding im-portance of DNA’s nucleotide sequence toboth its natural biological function as wellas the utility associated with DNA in itsisolated form. The preservation of thisdefining characteristic of DNA in its nativeand isolated forms mandates the conclu-sion that the challenged composition claimsare directed to unpatentable products ofnature.

Myriad argues that the § 101 inquiryinto the subject matter patentability ofisolated DNA should focus exclusively onthe differences alleged to exist betweennative and isolated DNA, rather than con-sidering the similarities that exist betweenthe two forms of DNA. See, e.g., MyriadReply at 8–9 (‘‘[T]he observation that iso-lated DNA and native DNA share thissingle property [i.e. the same protein cod-ing sequences] is irrelevant to the criticalissue of whether there are differences intheir properties. It is the differences thatare legally relevant to the novelty inquiryunder Section 101, not the properties heldin common.’’ (emphasis in original)); Myri-ad Br. at 8. Setting aside the fact thatconsiderations such as novelty are irrele-vant for § 101 purposes, see Bergy, 596F.2d at 960–61, Myriad offers no authori-ties supporting such an approach. To the

contrary, the Supreme Court has held that‘‘[i]n determining the eligibility of [a]claimed process for patent protection un-der § 101, [the] claims must be consideredas a whole.’’ Diehr, 450 U.S. at 188, 101S.Ct. 1048. Similarly, the Federal Circuithas expressly held that ‘‘[i]n the final anal-ysis under § 101, the claimed invention, asa whole, must be evaluated for what it is.’’In re Grams, 888 F.2d 835, 839 (Fed.Cir.1989) (quoting In re Abele, 684 F.2d 902,907 (C.C.P.A.1982)).

Were Myriad’s approach the law, it isdifficult to discern how any invention couldfail the test. For example, the bacterialmixture in Funk Brothers was unquestion-ably different from any preexisting bacter-ial mixture; yet the Supreme Court recog-nized that a patent directed to the mixture,considered as a whole, did no more thanpatent ‘‘the handiwork of nature.’’ 333U.S. at 131, 68 S.Ct. 440. There will al-most inevitably be some identifiable differ-ences between a claimed invention and aproduct of nature; the appropriate § 101inquiry is whether, considering the claimedinvention as a whole, it is sufficiently dis-tinct in its fundamental characteristicsfrom natural phenomena to possess therequired ‘‘distinctive name, character,[and] use.’’ Chakrabarty, 447 U.S. at 309–10, 100 S.Ct. 2204.

None of Myriad’s arguments establishthe distinctive nature of the claimed DNA.Myriad’s argument that association ofchromosomal proteins with native DNAestablishes the existence of ‘‘structural dif-ferences’’ between native and isolatedDNA relies on an incorrect comparisonbetween isolated DNA and chromatin,which are indeed different insofar as chro-matin includes chromosomal proteins nor-mally associated with DNA. The propercomparison is between the claimed isolatedDNA and the corresponding native DNA,and the presence or absence of chromo-


somal proteins merely constitutes a differ-ence in purity that cannot serve to estab-lish subject matter patentability. See Gen.Elec., 28 F.2d at 642–43; Marden I, 47F.2d at 957–58; Marden II, 47 F.2d at959.

Myriad also attempts to rely on its as-sertion that native DNA contains intronsequences that are absent in the claimedBRCA1/2 DNA. However, some of theclaims, such as claim 1 of the 8282 patent,are directed broadly to DNA ‘‘coding for aBRCA1 polypeptide.’’ Native BRCA1DNA, by definition, encodes the BRCA1protein; thus claim 1 of the 8282 patentwould cover purified BRCA1 DNA pos-sessing the exact same structure found inthe human cell, introns and all.52 See also8492 patent, claim 1 (similarly claiming iso-lated DNA ‘‘coding for a BRCA2 polypep-tide’’). In addition, several of the composi-tion claims are directed to isolated DNAcontaining as few as 15 nucleotides of theBRCA1 coding sequence, see, e.g., 8282 pat-ent, claims 5 & 6, and at least some ofthese short DNA sequences will be foundwithin a single exon of the native BRCA1gene sequence. See Adam Pavlicek, et al.,Evolution of the Tumor SuppressorBRCA1 Locus in Primates: Implicationsfor Cancer Predisposition, 13 Human Mo-lecular Genetics 2737, 2737 (2004) (notingBRCA1 exons range from 37 to 3427 nu-cleotides in length). Therefore, for thesesmall DNA fragments, the existence ofintrons in native BRCA1 DNA is complete-

ly irrelevant to the question of structuraldifferences when comparing these shortDNA molecules with native BRCA1 DNA.

More generally, the fact that theBRCA1/2 cDNA molecules covered by thecomposition claims-in-suit contain only theprotein coding exons and not the intronsfound in native DNA does not render thesecDNAs and their native counterparts‘‘markedly different.’’ The splice variantsrepresented by these cDNAs are the re-sult of the naturally-occurring splicing ofpre-mRNA into mature mRNA. Therefore,not only are the coding sequences con-tained in the claimed DNA identical tothose found in native DNA, the particulararrangement of those coding sequences isthe result of the natural phenomena ofRNA splicing. Finally, at least in the caseof BRCA1, the claimed cDNA sequencesare actually found in the human genome inthe form of a naturally occurring pseudo-gene. See Mason Supp. Decl. ¶ 18.53

Myriad’s argument that the functionaldifferences between native and isolatedDNA demonstrates that they are ‘‘marked-ly different’’ relies on the fact that isolatedDNA may be used in applications forwhich native DNA is unsuitable, namely, in‘‘molecular diagnostic tests (e.g., as probes,primers, templates for sequencing reac-tions), in biotechnological processes (e.g.production of pure BRCA1 and BRCA2protein), and even in medical treatments

52. To the extent a claim reads on unpatent-able subject matter, the entire claim must bedeemed invalid. See Titanium Metals Corp. ofAm. v. Banner, 778 F.2d 775, 782 (Fed.Cir.1985).

53. Native DNA is sometimes methylated, butthat methylation is preserved when the DNAis extracted and purified. Nussbaum Decl.¶ 20. Since the claimed ‘‘isolated DNA’’ in-cludes DNA extracted and purified from thebody, methylation of DNA in the body does

not distinguish native DNA from the claimedDNA. In addition, DNA in the body also existsin a non-methylated state, just as the synthe-sized DNA claimed in the patents would notbe methylated. More importantly, while me-thylation affects the transcription of a gene inthe body, it does not have any impact on thegenetic information contained within theDNA. Indeed, DNA is demethylated and reme-thylated as it passes from the germline of onegeneration to the next. Nussbaum Decl. ¶ 28.


(e.g. gene therapy).’’ Myriad Reply at 9;see also Myriad Br. at 30–32.

Isolated DNA’s utility as a primer or amolecular probe (for example, for South-ern blots) arises from its ability to ‘‘targetand interact with other DNA molecules,’’that is, the ability of a given DNA mole-cule to bind exclusively to a specific DNAtarget sequence. Myriad Br. at 33; seeKay Decl. ¶ 138. Thus, for example, a 24nucleotide segment of isolated BRCA1DNA can be used as a primer because itwill bind only to its corresponding locationin the BRCA1 gene. However, the basisfor this utility is the fact that the isolatedDNA possesses the identical nucleotide se-quence as the target DNA sequence,54 thusallowing target specific hybridization be-tween the DNA primer and the portion ofthe target DNA molecule possessing thecorresponding sequence. Kay Decl.¶¶ 135–36, 138. In contrast, another 24nucleotide segment of DNA possessing thesame nucleotide composition but a differ-ent nucleotide sequence would not havethe same utility because it would be unableto hybridize to the proper location in theBRCA1 gene.55 Indeed, Myriad implicitlyacknowledges this fact when it states thatthe usefulness of isolated DNA molecules‘‘is based on their ability to target andinteract with other DNA molecules, whichis a function of their own individual struc-ture and chemistry.’’ Myriad Br. at 33(emphasis added). Therefore, the citedutility of the isolated DNA as a primer orprobe is primarily a function of the nucleo-tide sequence identity between native andisolated BRCA1/2 DNA.

Similarly, the utility of isolated DNA asa sequencing target relies on the preserva-tion of native DNA’s nucleotide sequence.Indeed, one need look no further thanMyriad’s BRACAnalysis testing, which re-lies on the sequencing of isolated DNA (i.e.the PCR amplified exons of BRCA1/2 ), todetermine the sequence of the correspond-ing DNA coding sequences found in thecell. The entire premise behind Myriad’sgenetic testing is that the claimed isolatedDNA retains, in all relevant respects, theidentical nucleotide sequence found in na-tive DNA. The use of isolated BRCA1/2DNA in the production of BRCA1/2 pro-teins or in gene therapy also relies on theidentity between the native DNA se-quences and the sequences contained inthe isolated DNA molecule. Were the iso-lated BRCA1/2 sequences different in anysignificant way, the entire point of theiruse—the production of BRCA1/2 pro-teins—would be undermined.

While the absence of proteins and othernucleotide sequences is currently requiredfor DNA to be useful for the cited pur-poses, the purification of native DNA doesnot alter its essential characteristic—itsnucleotide sequence—that is defined bynature and central to both its biologicalfunction within the cell and its utility as aresearch tool in the lab. The requirementthat the DNA used be ‘‘isolated’’ is ulti-mately a technological limitation to the useof DNA in this fashion, and a time maycome when the use of DNA for molecularand diagnostic purposes may not requiresuch purification. The nucleotide se-quence, however, is the defining character-istic of the isolated DNA that will always

54. To be precise, the isolated single-strandedDNA molecule utilized as a primer or probehas the identical sequence as the complemen-tary DNA strand to the DNA strand contain-ing the target DNA sequence. The descrip-tion in the text is meant to serve as a short-hand description of this relationship.

55. The same reasoning applies with respect tothe use of isolated DNA as a probe. See KayDecl. ¶¶ 135–36.


be required to provide the sequence-specif-ic targeting and protein coding ability thatallows isolated DNA to be used for thevarious applications cited by Myriad. Forthese reasons, the use of isolated DNA forthe various purposes cited by Myriad doesnot establish the existence of differences‘‘in kind’’ between native and isolated DNAthat would establish the subject matterpatentability of what is otherwise a prod-uct of nature. See Am. Fruit Growers,283 U.S. at 11, 51 S.Ct. 328.

Finally, the isolated BRCA1/2 DNAclaimed in Myriad’s patents bears compari-son to the bacterial mixture in FunkBrothers. In explaining why the claimedmixture of bacteria did not constitute aninvention, the Court observed that the firstpart of the claimed invention was the‘‘[d]iscovery of the fact that certain strainsof each species of these bacteria can bemixed without harmful effect to the prop-erties of either’’ which was ‘‘a discovery oftheir qualities of non-inhibition. It is nomore than the discovery of some of thehandiwork of nature and hence is not pat-entable.’’ 333 U.S. at 131, 68 S.Ct. 440.The Court went on to observe that thesecond part of the claimed invention was‘‘[t]he aggregation of select strains of theseveral species into one product[,] an appli-cation of that newly-discovered naturalprinciple. But however ingenious the dis-covery of that natural principle may havebeen, the application of it is hardly morethan an advance in the packaging of theinoculants.’’ Id.

According to Myriad, the inventionclaimed in its patents required the identifi-cation of the specific segments of chromo-somes 17 and 13 that correlated withbreast and ovarian cancer (BRCA1 andBRCA2 ) followed by the isolation of thesesequences away from other genomic DNAand cellular components. Myriad Reply at6 (‘‘By identifying these particular BRCA

DNAs and isolating them away from othergenomic DNA and other cellular compo-nents, the inventors created the claimedisolated BRCA DNA molecules.’’). Likethe discovery of the mutual non-inhibitionof the bacteria in Funk Brothers, discov-ery of this important correlation was adiscovery of the handiwork of nature—thenatural effect of certain mutations in aparticular segment of the human genome.And like the aggregation of bacteria inFunk Brothers, the isolation of the BRCA1and BRCA2 DNA, while requiring techni-cal skill and considerable labor, was simplythe application of techniques well-known tothose skilled in the art. See Parthasara-thy Decl. ¶ 19. The identification of theBRCA1 and BRCA2 gene sequences is un-questionably a valuable scientific achieve-ment for which Myriad deserves recogni-tion, but that is not the same as concludingthat it is something for which they areentitled to a patent. See Funk Bros., 333U.S. at 132, 68 S.Ct. 440 (‘‘[O]nce nature’ssecret of the non-inhibitive quality of cer-tain strains of the [nitrogen-fixing bacte-ria] was discovered, the state of the artmade the production of a mixed inoculant asimple step. Even though it may havebeen the product of skill, it certainly wasnot the product of invention.’’).

Because the claimed isolated DNA is notmarkedly different from native DNA as itexists in nature, it constitutes unpatentablesubject matter under 35 U.S.C. § 101.

D. The Method Claims are InvalidUnder 35 U.S.C. § 101

[12, 13] ‘‘Phenomena of nature, thoughjust discovered, mental processes, and ab-stract intellectual concepts are not patent-able, as they are the basic tools of scienti-fic and technological work.’’ Benson, 409U.S. at 67, 93 S.Ct. 253. However, ‘‘ ‘anapplication of a law of nature or mathe-matical formula to a known structure or


process may well be deserving of patentprotection.’ ’’ Bilski, 545 F.3d at 953(quoting Diehr, 450 U.S. at 187, 101 S.Ct.1048). In Bilski, the Federal Circuit setforth ‘‘the definitive test to determinewhether a process claim is tailored nar-rowly enough to encompass only a particu-lar application of a fundamental principlerather than pre-empt the principle itself.’’Id. at 954. Under this ‘‘machine or trans-formation’’ test, ‘‘[a] claimed process issurely patent-eligible under § 101 if: (1) itis tied to a particular machine or appara-tus, or (2) it transforms a particular articleinto a different state or thing.’’ Id. Inaddition, ‘‘the use of a specific machine ortransformation of an article must imposemeaningful limits on the claim’s scope toimpart patent-eligibility,’’ and ‘‘the involve-ment of the machine or transformation inthe claimed process must not merely beinsignificant extra-solution activity.’’ Id.at 961–62. In other words, the ‘‘transfor-mation must be central to the purpose ofthe claimed process.’’ Id. at 962. In par-ticular, the Bilski court held that ‘‘addinga data-gathering step to an algorithm isinsufficient to convert that algorithm into apatent-eligible process.’’ Id. at 963 (citingGrams, 888 F.2d at 840; Meyer, 688 F.2dat 794). ‘‘A requirement simply that datainputs be gathered—without specifyinghow—is a meaningless limit on a claim toan algorithm because every algorithm in-herently require the gathering of data in-puts.’’ Id. (citing Grams, 888 F.2d at 839–40). ‘‘Further, the inherent step of gath-ering data can also fairly be characterizedas insignificant extra-solution activity.’’Id. (citing Flook, 437 U.S. at 590, 98 S.Ct.2522).

1. The claims for ‘‘analyzing’’ and‘‘comparing’’ DNA sequences

are invalid under § 101

[14] Claim 1 of the 8999 patent is di-rected to the process of ‘‘analyzing’’ a

BRCA1 sequence and noting whether ornot the specified naturally-occurring muta-tions exist. The claimed process is notlimited to any particular method of analy-sis and does not specify any further actionbeyond the act of ‘‘analyzing.’’ Similarly,claim 1 of the 8001, 8441, and 8857 patentsas well as claim 2 of the 8857 patents aredirected to ‘‘comparing’’ two gene se-quences to see if any differences exist anddo not specify any limitations on the meth-od of comparison.

Myriad argues that these method claimsshould not be viewed as mental processesbecause they incorporate a transformationstep and therefore satisfy the ‘‘transfor-mation’’ prong of the Bilski ‘‘machine ortransformation’’ test. In support of itsposition, Myriad relies primarily on theFederal Circuit’s holding in Prometheus,581 F.3d 1336. There, the Federal Circuitconsidered a patent containing claims di-rected to methods for calibrating theproper dosage of thiopurine drugs bymeasuring metabolites in subjects havinggastrointestinal disorders. Id. at 1343–50.The patentees had discovered a correla-tion between metabolite levels in a pa-tient’s blood and the therapeutic efficacyof a dose of the drug. Based on this cor-relation, the patentees claimed methods tooptimize therapeutic efficiency while mini-mizing side effects by determining meta-bolite levels and identifying a need to ad-just drug dosage upward or downwardbased on the levels. Id. at 1339–40. Arepresentative claim asserted by the pat-entee in Prometheus claimed:

A method of optimizing therapeutic effi-cacy for treatment of an immune-me-diated gastrointestinal disorder, com-prising:

(a) administering a drug providing 6–thioguanine to a subject having saidimmune-mediated gastrointestinal dis-order; and


(b) determining the level of 6–thiogua-nine in said subject having said im-mune-mediated gastrointestinal disor-der,

wherein the level of 6–thioguanine lessthan about 230 pmol per 8x10 8 redblood cells indicates a need to increasethe amount of said drug subsequentlyadministered to said subject and

wherein the level of 6–thioguanine great-er than about 400 pmol per 8xl0 8 redblood cells indicates a need to de-crease the amount of said drug subse-quently administered to said subject.

Id. at 1340.

In concluding that the claimed methodssatisfied the requirements of § 101, theFederal Circuit held that the relevanttransformation for purposes of the ‘‘ma-chine or transformation’’ test was thetransformation of the human body as wellas the chemical and physical changes ofthe drug’s metabolites. Id. at 1346 (stat-ing that ‘‘claims to methods of treatment,’’were ‘‘always transformative when a de-fined group of drugs is administered to thebody to ameliorate the effects of an unde-sired condition’’). Because the transfor-mative steps were central to the claimedtreatment methods, they satisfied the ‘‘ma-chine or transformation’’ test. Id. at 1346–47. The court went on to hold that the‘‘determining’’ step alone was transforma-tive and central to the claimed methodssince ‘‘determining the levels of [the meta-bolites] 6–TG or 6–MMP in a subject nec-essarily involves a transformation, forthose levels cannot be determined by mereinspection.’’ Id. at 1347.

Myriad argues that just as the act of‘‘determining’’ metabolite levels in Prome-theus was found to involve the transfor-mation of human blood, so too should ‘‘an-alyzing’’ or ‘‘comparing’’ BRCA1/2 genesequences be construed to incorporatephysically transformative steps (i.e. theisolation and sequencing of DNA 56) thatwould satisfy the Bilski ‘‘machine ortransformation’’ test. Myriad further as-serts that these transformations are ‘‘cen-tral to the purpose of the claims,’’ id. at1347, because ‘‘Myriad’s method claimseach require the transformation of a tis-sue or blood sample in order to isolate thepatient’s DNA.’’ Myriad Br. at 35.

The claims in Prometheus, however, aredistinguishable from the method claims indispute here. In Prometheus, ‘‘determin-ing metabolite levels in the clinical samplestaken from patients’’ was found to betransformative because the act of ‘‘deter-mining metabolite levels’’ was itself con-strued to include the extraction and meas-urement of metabolite concentrations, suchas high pressure liquid chromatography.See Prometheus, 581 F.3d at 1347. In-deed, neither party in Prometheus disput-ed that ‘‘determining’’ metabolite levels insamples taken from patients was, in and ofitself, transformative.57 Id.

In contrast, the language of the methodclaims-in-suit and the plain and ordinarymeanings of the terms ‘‘analyzing’’ or‘‘comparing’’ establish that the methodclaims-in-suit are directed only to the ab-stract mental processes of ‘‘comparing’’ or‘‘analyzing’’ gene sequences. AlthoughMyriad asserts that the challenged methodclaims are directed to comparing DNAmolecules rather than DNA sequences, the

56. The challenged method claims are also di-rected to analyzing and comparing RNA andcDNA sequences, but for purposes of thisopinion, the discussion will be framed interms of analyzing and comparing DNA se-quences.

57. The issue with respect to the ‘‘determin-ing’’ step was not whether it was transforma-tive, but whether that transformation wascentral to the claimed invention. Id.


language of the claims belies such an inter-pretation. While the purpose of theclaimed method is, for example, to ‘‘detecta germline alteration in a BRCA1 gene,’’see 8999 patent, col. 161:17–18, the methodactually claimed is ‘‘analyzing a sequenceof a BRCA1 gene.’’ 8999 patent, col. 161:20–21 (emphasis added); see also 8001 pat-ent, col. 144:2–17 (‘‘A method TTT whichcomprises gene comparing a first sequenceselected from the group consisting of aBRCA1 gene from said tumor sample TTT

with a second sequence selected from thegroup consisting of BRCA1 gene from anontumor sample TTT wherein a differencein the sequence of the BRCA1 gene TTT

indicates a somatic alteration in theBRCA1 gene.’’); 8857 patent, col. 169:40–45 (‘‘A method TTT which comprises com-paring the nucleotide sequence of the sus-pected mutant BRCA2 allele with the wild-type BRCA2 nucleotide sequence TTTT’’).

Similarly, the inclusion of the phrases‘‘from a human subject’’ or ‘‘from a nontu-mor sample’’ in the claims serve only tospecify the identity of the DNA or RNAsequence to be ‘‘analyzed’’ or ‘‘compared,’’i.e., from a human sample as opposed to ananimal sample or cell culture, and do not,as Myriad argues, establish that the claimsshould be read to include the physicaltransformations associated with obtainingDNA from those sources.58 In addition,the passages from the 8999 specificationcited by Myriad describing the process by

which DNA sequences are obtained cannotserve to redefine the scope of the chal-lenged claims without violating the prohi-bition against importing claim limitationsfrom the specification. See Phillips, 415F.3d at 1320.

By the same token, the transformativesteps associated with isolating and se-quencing DNA described in the unchal-lenged dependent claims cannot be used toestablish that the challenged claims in-clude transformative events. To do sowould violate the doctrine of claim differ-entiation, which presumes that ‘‘differentwords or phrases used in separate claimsTTT indicate that the claims have differentmeanings and scope.’’ Karlin Tech., Inc.v. Surgical Dynamics, Inc., 177 F.3d 968,972 (Fed.Cir.1999). Because claim differ-entiation ‘‘prevents the narrowing of broadclaims by reading into them the limitationsof narrower claims,’’ Clearstream Waste-water Sys., Inc. v. Hydro–Action, Inc., 206F.3d 1440, 1446 (Fed.Cir.2000), the depen-dent claims serve only to illustrate thebreadth of the challenged claims and rein-force the conclusion that what is claimedare mental processes independent of anyphysical transformations. See Phillips,415 F.3d at 1314–15 (‘‘[T]he presence of adependent claim that adds a particular lim-itation gives rise to a presumption that thelimitation in question is not present in theindependent claim.’’).59

58. Whether acts are ‘‘transformative’’ in thecontext of the ‘‘machine or transformation’’test for process claims is distinct from thequestion of whether those acts would renderthe resulting product patentable subject mat-ter. See, e.g., Am. Wood–Paper, 90 U.S. (23Wall.) at 593–94 (noting that a party may beentitled to a patent on a process for purifyinga natural product but not the final productitself if the final product is not different ‘‘inkind’’ from the natural product); Merz, 97F.2d at 601 (same). Therefore the descriptionof DNA purification and sequencing as‘‘transformative acts’’ in the context of the

challenged process claims is not inconsistentwith the conclusion that the isolated DNAsclaimed in the challenged patents constituteunpatentable subject matter.

59. The patent examiner’s reasons for allow-ance, cited by Myriad, are precisely the legalconclusions concerning the patentability ofthe claimed methods being challenged byPlaintiffs. Moreover, the examiner’s reasonsof allowance cannot serve to define the scopeof claim terms. See ACCO Brands, Inc. v.Micro Sec. Devices, Inc., 346 F.3d 1075, 1079(Fed.Cir.2003).


Myriad also argues that because isolat-ing and sequencing DNA are required for‘‘analyzing’’ or ‘‘comparing’’ DNA se-quences, Prometheus allows those trans-formative acts to be incorporated into theprocess claims for purposes of the § 101analysis. See Myriad Reply at 12. Myri-ad thus seeks to rely on transformationsnot actually claimed by the method claims-in-suit to satisfy the Bilski ‘‘machine ortransformation’’ test. Neither Prometheusnor any other authority supports such anexpansive approach to the application ofthis test. Prometheus held only that theterm ‘‘determining,’’ as used in the claimsat issue, referred to acts that includedmanipulations that satisfied the ‘‘machineor transformation’’ test. Id. Nowhere didPrometheus suggest that preparatoryphysical transformations required for theperformance of, but not included in, claimsdirected to mental processes should beincorporated into the claim for purposes ofthe § 101 analysis. Not only would suchan approach be inconsistent with the pro-hibition on the importation of claim limita-tions from the specification, it would effec-tively vitiate the limitations to claimingmental processes provided by the ‘‘ma-chine or transformation’’ test since ‘‘to usevirtually any natural phenomenon for vir-tually any useful purpose could well in-volve the use of empirical information ob-tained through an unpatented means thatmight have involved transforming matter.’’Metabolite Labs., 548 U.S. at 136, 126S.Ct. 2921 (Breyer, J., dissenting). There-fore the preparatory transformations relat-ing to obtaining DNA sequences cannot berelied on to satisfy the requirements of§ 101.

Even if the challenged method claimswere read to include the transformationsassociated with isolating and sequencinghuman DNA, these transformations wouldconstitute no more than ‘‘data-gatheringstept[s]’’ that are not ‘‘central to the pur-

pose of the claimed process.’’ Bilski, 545F.3d at 962–63. In Grams, the FederalCircuit considered a patent directed to amethod of diagnosing an abnormal condi-tion in an individual. The claimed methodconsisted of two steps: (1) ‘‘performance ofclinical laboratory tests on an individual toobtain data for the parameters,’’ and (2)‘‘analyz[ing] that data to ascertain the exis-tence and identity of an abnormality TTTT’’888 F.2d at 837. Concluding that the es-sence of what was claimed was the mathe-matical algorithm for analyzing the clinicaldata, and that the sole physical process—laboratory testing—was merely data-gath-ering to obtain clinical data, the court heldthe patent invalid under § 101 for claiminga mathematic algorithm. Id. at 840.

The method claims-in-suit present aclosely analogous situation. The essenceof what is claimed is the identification of apredisposition to breast cancer based on‘‘analyzing’’ or ‘‘comparing’’ BRCA1/2 genesequences. See, e.g., 8857 patent, claim 2(‘‘A method for diagnosing a predispositionfor breast cancer in a human subject whichcomprises comparing the [BRCA2 gene se-quence] from said subject with the [ ] se-quence of the wild-type BRCA2geneTTTT’’). As in Grams, isolation andsequencing of DNA from a human sample,even if incorporated into the methodclaims-in-suit, would represent nothingmore than data-gathering steps to obtainthe DNA sequence information on which toperform the claimed comparison or analy-sis. Moreover, in the absence of a speci-fied method for isolating and sequencingDNA, ‘‘[a] requirement simply that datainputs be gathered—without specifyinghow—is a meaningless limit on a claim toan algorithm because every algorithm in-herently requires the gathering of datainputs.’’ Bilski, 545 F.3d at 963 (citingGrams, 888 F.2d at 839–40). Consequent-ly, even if the method claims-in-suit were


construed to include the physical transfor-mations associated with isolating and se-quencing DNA, they would still fail the‘‘machine or transformation’’ test under§ 101 for subject matter patentability.

2. The claim for ‘‘comparing’’the growth rate of cells is

invalid under § 101.

[15] Claim 20 of the 8282 patent isdirected to ‘‘comparing’’ the growth ratesof cells in the presence or absence of apotential cancer therapeutic. Specifically,the claim recites a method for identifyingpotential cancer therapeutics by utilizingcells into which an altered BRCA1 geneknown to cause cancer has been inserted.Thus modified to mimic cancerous cells inthe body, these cells are then grown ineither the presence or absence of a poten-tial cancer therapeutic, and the growthrates of the cells are compared to deter-mine the effect of the potential therapeu-tic.

Unlike the method claims directed to‘‘analyzing’’ or ‘‘comparing’’ DNA se-quences, claim 20 arguably recites certaintransformative steps, such as the adminis-tration of the test compound.60 However,the essence of the claim, when consideredin its entirety, is the act of comparing cell

growth rates and concluding that ‘‘a slowergrowth of said host cell in the presence ofsaid compound is indicative of a cancertherapeutic.’’ 8282 patent, col. 156:25–27.

This claimed ‘‘process’’ is, in fact, thescientific method itself, and claim 20 seeksto patent a basic scientific principle: that aslower rate of cell growth in the presenceof a compound indicates that the com-pound may be a cancer therapeutic. Therecited transformative steps, as in Grams,represent nothing more than preparatory,data-gathering steps to obtain growth rateinformation and do not render the claimedmental process patentable under § 101.See Grams, 888 F.2d at 840 (‘‘The pres-ence of a physical step in the claim toderive data for the algorithm will not ren-der the claim statutory’’).61

E. The Constitutional ClaimsAgainst the USPTO Are Dis-missed

[16] As determined above, the patentsissued by the USPTO are directed to a lawof nature and were therefore improperlygranted. The doctrine of constitutionalavoidance, which states that courts shouldnot reach unnecessary constitutional ques-tions, thereby becomes applicable. See,

60. It is questionable whether the two trans-formations cited by Myriad are relevant trans-formations for purposes of the § 101 inquiry.Under Prometheus, the administration of atest compound is transformative only if iteffects a change in cell growth. See Prome-theus, 581 F.3d at 1346 (finding ‘‘administer-ing’’ of a drug transformative since it resultedin changes to both the patient and the drugmetabolites). If the test compound had noeffect on the cells, it is unclear whether therewould be any basis to view its administrationas working a ‘‘transformation’’ since therewould be no transformation with respect tothe cells (i.e. there was no change in theirgrowth rate) and there would also presumablybe no transformation with respect to the testdrug (i.e. it was not metabolized).

The other alleged ‘‘transformation’’ cited byMyriad is the insertion of DNA into cells tocreate the ‘‘transformed eukaryotic cell’’ fortreatment with the test compound. Kay Decl.¶ 57. Even more that its expansive interpre-tation of the method claims for analyzingDNA sequences for § 101 purposes. Myriad’sattempt to rely on transformations associatedwith the creation of a starting product for itsclaimed process is unsupported by the lawand demonstrates the limitlessness of Myri-ad’s interpretation of Prometheus and the‘‘machine or transformation’’ test.

61. Because Plaintiffs’ motion for summaryjudgment with respect to its claims againstMyriad is granted on the basis of 35 U.S.C.§ 101, its Constitutional claims need not beaddressed.


e.g., Allstate Ins. Co. v. Serio, 261 F.3d143, 149–50 (2d Cir.2001) (‘‘It is axiomaticthat the federal courts should, where pos-sible, avoid reaching constitutional ques-tions.’’) (citing Spector Motor Serv., Inc. v.McLaughlin, 323 U.S. 101, 65 S.Ct. 152, 89L.Ed. 101 (1944) (‘‘If there is one doctrinemore deeply rooted than any other in theprocess of constitutional adjudication, it isthat we ought not to pass on questions ofconstitutionality TTT unless such adjudica-tion is unavoidable’’)); see also Ashwanderv. TVA, 297 U.S. 288, 347, 56 S.Ct. 466, 80L.Ed. 688 (1936) (Brandeis, J., concurring)(‘‘[I]f a case can be decided on either oftwo grounds, one involving a constitutionalquestion, the other a question of statutoryconstruction or general law, the Court willdecide only the latter.’’). This doctrinebears on the consideration of Plaintiffs’claims that the USPTO’s policy permittingthe grant of the Myriad patents violatesArticle I, Section 8, Clause 8 and the FirstAmendment of the Constitution.

The Plaintiffs have not addressed theseauthorities and have contended that ‘‘thedoctrine of constitutional avoidance is inap-plicable’’ because the invalidation of Myri-ad’s claims pursuant to 35 U.S.C. § 101‘‘will not necessarily invalidate the USP-TO’s policy [in granting the patents].’’ Pl.Reply at 43. However, a decision by theFederal Circuit or the Supreme Court af-firming the holding set forth above wouldapply to both the issued patents as well aspatent applications and would be bindingon all patent holders and applicants, aswell as the USPTO. See KoninklijkePhilips Electronics N.V. v. Cardiac Sci-ence, 590 F.3d 1326, 1337 (Fed.Cir.2010)(‘‘We remind the district court and the[USPTO] Board that they must follow ju-dicial precedent TTTT’’). Thus, to the ex-tent the USPTO examination policies areinconsistent with a final, binding ruling,the USPTO would conform its examinationpolicies to avoid issuing patents directed to

isolated DNA or the comparison or analy-sis of DNA sequences. See USPTO ReplyMemo, at 4.

With the holding that the patents areinvalid, the Plaintiffs have received therelief sought in the Complaint and thedoctrine of constitutional avoidance pre-cludes this Court from reaching the consti-tutional claims against the USPTO. SeeAllstate Ins. Co. v. Serio, 261 F.3d 143,149–50 (2d Cir.2001); USPTO Br. at 4.Plaintiffs’ claims for constitutional viola-tions against the USPTO are thereforedismissed without prejudice.

VI. CONCLUSION

For the reasons set forth above, Plain-tiffs’ motion for summary judgment isgranted in part, Myriad’s motion for sum-mary judgment is denied, the USPTO’smotion for judgment on the pleadings isgranted, and the claims-in-suit are de-clared invalid pursuant to 35 U.S.C. § 101.

Submit judgment on notice.

It is so ordered.

,

PERNOD RICARD USALLC, Plaintiff,

v.

BACARDI U.S.A., INC., Defendant.

No. Civ. No. 06–505–SLR.

United States District Court,D. Delaware.

April 6, 2010.

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