No. 09-

In the Supreme Court of the United States

MAYO COLLABORATIVE SERVICES (D/B/A MAYO

MEDICAL LABORATORIES) AND MAYO CLINIC

ROCHESTER,

Petitioners,

v.

PROMETHEUS LABORATORIES, INC.,

Respondent.

Petition for a Writ of Certiorari to the UnitedStates Court of Appeals for the Federal Circuit

PETITION FOR A WRIT OF CERTIORARI

JONATHAN E. SINGER

JOHN A. DRAGSETH

Fish & Richardson P.C.3200 RBC Plaza60 South 6th StreetMinneapolis, MN 55402(612) 335-5070

EUGENE VOLOKH

405 Hilgard AvenueLos Angeles, CA 90095

STEPHEN M. SHAPIRO

Counsel of RecordTIMOTHY S. BISHOP

JEFFREY W. SARLES

Mayer Brown LLP71 South Wacker DriveChicago, IL 60606(312) 782-0600

Counsel for Petitioners

QUESTION PRESENTED

The Federal Circuit, reversing the district court,upheld Prometheus’s patent claims covering a pro-cess for correlating the level of certain chemicals in apatient’s blood with the patient’s health. By thoseclaims, Prometheus seeks to monopolize the use ofblood tests in the research, diagnosis, and treatmentof disease, such that a physician violates the patentmerely by thinking about the correlation between thetest results and the patient’s health or treatment.This Court granted certiorari to determine whetherbasic scientific relationships may be monopolized inthis way in Laboratory Corp. of Am. Holdings v.Metabolite Labs., Inc., 548 U.S. 124, 135 (2006)(“LabCorp”), but dismissed the writ for lack ofadequate issue preservation. Dissenting from dismis-sal, Justices Breyer, Stevens, and Souter explainedthat such patents are invalid under this Court’sprecedents, and that resolving the issue presented inLabCorp was of great importance to innovativescientific inquiry and effective medical research andtreatment.

The question presented is as follows:

Whether 35 U.S.C. § 101 is satisfied by a patentclaim that covers observed correlations betweenpatient test results and patient health, so that theclaim effectively preempts all uses of these naturallyoccurring correlations.

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RULES 14.1(b) AND 29.6 STATEMENT

All parties are identified in the caption of thispetition. Petitioner Mayo Collaborative Services, asubsidiary of Mayo Clinic, is a for-profit Minnesotacorporation that provides reference laboratoryservices under the name Mayo Medical Laboratories.Petitioner Mayo Clinic Rochester, a subsidiary ofMayo Clinic, is a charitable, nonprofit corporationlocated in Rochester, Minnesota. No publicly heldcompany owns 10% or more of the stock of eitherpetitioner.

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TABLE OF CONTENTS

Page

QUESTION PRESENTED..........................................i

RULES 14.1(b) AND 29.6 STATEMENT................. ii

TABLE OF AUTHORITIES......................................vi

OPINIONS BELOW...................................................1

JURISDICTION .........................................................1

STATUTORY PROVISIONS INVOLVED ................1

INTRODUCTION.......................................................2

STATEMENT .............................................................3

A. Prometheus’s Sweeping PatentClaims....................................................3

B. The District Court’s DecisionInvalidating The Patents......................8

C. The Federal Circuit’s DecisionUpholding The Patents.......................11

REASONS FOR GRANTING THE PETITION ......13

I. THE FEDERAL CIRCUIT’S ELEVA-TION OF ITS “MACHINE OR TRANS-FORMATION” TEST TO THE SINGLEDETERMINANT OF PATENTABILITYCONFLICTS WITH THIS COURT’SPREEMPTION STANDARD.........................13

A. The Court has long invalidatedpatent claims that attempt topreempt all uses of a naturalphenomenon ........................................13

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TABLE OF CONTENTS—continued

Page

B. Prometheus’s claims are invalidbecause they preempt all uses ofthe natural correlation betweenpatient metabolite levels andpatient health......................................14

C. The Federal Circuit improperlyapplied its “machine or trans-formation” test in place of thisCourt’s preemption standard .............19

II. CERTIORARI SHOULD BE GRANTEDTO RESOLVE THE IMPORTANTQUESTION LEFT UNRESOLVED INLABCORP ......................................................22

CONCLUSION .........................................................28

APPENDIX A: Opinion of the United States Courtof Appeals for the Federal Circuit(Sept. 16, 2009) .................................................1a

APPENDIX B: Order granting defendants’ motionfor summary judgment of patent invaliditypursuant to 35 U.S.C. § 101 [Doc. #502](S.D. Cal. Mar. 28, 2008) .................................26a

APPENDIX C: Order denying defendants’ motionfor summary judgment [Doc #14] and grantingplaintiff’s cross-motion for summary judgmenton patent infringement [Doc. #135] (S.D. Cal.Nov. 21, 2005) .................................................60a

v

TABLE OF CONTENTS—continued

Page

APPENDIX D: Final Judgment (S.D. Cal.May 16, 2008) .................................................94a

vi

TABLE OF AUTHORITIES

Page

CASES

Ashcroft v. Free Speech Coalition,535 U.S. 234 (2002)............................................. 27

Bilski, In re,545 F.3d 943 (Fed. Cir. 2008) (en banc),cert. granted, 129 S. Ct. 2735 (2009)...........passim

Cochrane v. Deener,94 U.S. 780 (1876)................................... 19, 20, 21

Diamond v. Chakrabarty,447 U.S. 303 (1980)....................................... 13, 14

Diamond v. Diehr,450 U.S. 175 (1981)......................................passim

eBay Inc. v. MercExchange, L.L.C.,547 U.S. 388 (2006)............................................. 22

Ferguson, In re,558 F.3d 1359 (Fed. Cir. 2009) ........................... 12

Funk Bros. Seed Co. v. Kalo Inoculant Co.,333 U.S. 127 (1948)....................................... 14, 18

Gottshalk v. Benson,409 U.S. 63 (1972)........................................passim

Graham v. John Deere Co.,383 U.S. 1 (1962)................................................. 22

vii

TABLE OF AUTHORITIES—continued

Page

KSR Int’l Co. v. Teleflex, Inc.,550 U.S. 398 (2007)............................................. 22

Laboratory Corp. of America Holdings v.Metabolite Laboratories, Inc.,548 U.S. 124 (2006) .....................................passim

Medimmune, Inc. v. Genentech, Inc.,549 U.S. 118 (2007)............................................. 22

Merck KGaA v. Integra Lifesciences I, Ltd.,545 U.S. 193 (2005)............................................. 23

New York v. Ferber,458 U.S. 747 (1982)............................................. 27

Parker v. Flook,437 U.S. 584 (1978)....................... 11, 16-17, 20-21

CONSTITUTION AND STATUTES

U.S. CONST. amend. I ......................................... 27, 28

28 U.S.C. § 1254(1)..................................................... 1

28 U.S.C. § 1295 ....................................................... 23

35 U.S.C. § 100(b)....................................................... 1

35 U.S.C. § 101 ..................................... 1, 9, 13, 21, 23

35 U.S.C. § 284 ......................................................... 28

viii

TABLE OF AUTHORITIES—continued

Page

OTHER AUTHORITIES

M. Boldrin & D. Levine, AGAINST

INTELLECTUAL MONOPOLY (2009) ....................... 25

L. Branstetter, Do Stronger Patents InduceMore Local Innovation?, 7 J. INT’L ECON.L. 359 (2004) ....................................................... 26

S. Breyer, The Uneasy Case for Copyright, 84HARV. L. REV. 281 (1970) .................................... 26

W. Landes & R. Posner, THE ECONOMIC

STRUCTURE OF INTELLECTUAL PROPERTY

LAW (2003)........................................................... 26

L. Lessig, THE FUTURE OF IDEAS (2001)................... 26

R. Merges & R. Nelson, On the ComplexEconomics of Patent Scope, 90 COLUM. L.REV. 839 (1990) ................................................... 26

A. Torrance & B. Tomlinson, Patents and theRegress of Useful Arts, 10 COLUM. SCI. &TECH. L. REV. 130 (2009)..................................... 26

PETITION FOR A WRIT OF CERTIORARI

Petitioners, Mayo Collaborative Services (d/b/aMayo Medical Laboratories) and Mayo ClinicRochester (collectively, “Mayo”), respectfully petitionfor a writ of certiorari to review the judgment of theUnited States Court of Appeals for the FederalCircuit.

OPINIONS BELOW

The court of appeals’ opinion (App., infra, 1a-25a)is reported at ___ F.3d ___, 2009 WL 2950232 (Fed.Cir. 2009). The district court’s opinion (App., infra,26a-59a) is reported at 2008 WL 878910 (S.D. Cal.Mar. 28, 2008).

JURISDICTION

The court of appeals entered its judgment onSeptember 16, 2009. The jurisdiction of this Court isinvoked under 28 U.S.C. § 1254(1).

STATUTORY PROVISIONS INVOLVED

“Whoever invents or discovers any new anduseful process, machine, manufacture, or compos-ition of matter, or any new and useful improvementthereof, may obtain a patent therefor, subject to theconditions and requirements of this title.” 35 U.S.C.§ 101.

“The term ‘process’ means process, art or method,and includes a new use of a known process, machine,manufacture, composition of matter, or material.” 35U.S.C. § 100(b).

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INTRODUCTION

This Court previously granted certiorari on theissue presented in this case in Laboratory Corp. ofAmerica Holdings v. Metabolite Laboratories, Inc.,548 U.S. 124, 135 (2006) (“LabCorp”), but could notresolve the merits because petitioner there had notpreserved the issue. The patent claims in LabCorpand Prometheus’s claims here both attempt toexclude the public from using the results of basichuman metabolic testing in the research, diagnosis,and treatment of disease. They do so by claimingprotection for the process of recognizing a correlationbetween the level of certain chemicals in thepatient’s blood and the patient’s health. In bothcases, the claims are silent as to what should be donewith such correlations and as a result purport tocover and thus preempt all possible uses of thebiological correlations.

Applying this Court’s case law invalidatingpatent claims that preempt all uses of a fundamentalscientific principle, the three Justices who dissentedfrom the dismissal of LabCorp as improvidentlygranted reasoned that the claims at issue wereobviously invalid and not even “at the boundary” ofpatentability. The district court here reached thesame conclusion with respect to Prometheus’s claims.The Federal Circuit reversed without even consider-ing the reasoning in LabCorp, using a newly minted“machine or transformation” test in place of thisCourt’s established standards for patentability.

This Court should review the Federal Circuit’serroneous decision, which is inconsistent with thisCourt’s precedent and with the reasoning of threeJustices in LabCorp. As reflected in the grant ofcertiorari in LabCorp, the 20 amicus filings in that

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case, and the seven amicus filings in the FederalCircuit here, the issue is one of exceptional publicimportance. Justices Breyer, Stevens, and Souterexplained that “special public interest consider-ations” are implicated by the question presentedbecause overbroad patents will “inhibit doctors fromusing their best medical judgment,” “force doctors tospend unnecessary time and energy to enter intolicense agreements,” “divert resources” from health-care tasks to “the legal task of searching patentfiles,” and “raise the cost of health care whileinhibiting its effective delivery.” 548 U.S. at 138.These considerations again warrant this Court’sreview, which may now proceed without theproblems that prevented resolution in LabCorp.

STATEMENT

A. Prometheus’s Sweeping Patent Claims

Prometheus’s broad patent claims attempt toturn a physician’s thought processes into infringe-ment. Specifically, the claims encompass a physi-cian’s mental determinations when evaluating apatient who has been given a thiopurine drug.1

Enzymes in the human body metabolize such drugsnaturally into metabolites that are therapeuticallyactive. App., infra, 41a. Low levels of such meta-bolites indicate an insufficient dose of the drug,whereas high levels indicate too much. These factshave been understood by physicians for decades, asthe Prometheus patents concede. See, e.g., ’623

1 U.S. Patents 6,355,623 (“the ’623 patent”) and6,680,302 (“the ’302 patent”), reproduced at C.A.App. A10001 and A10019, are also available athttp://tiny.cc/y867p and http://tiny.cc/TR2FY, res-pectively.

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Patent at 8:37-39, C.A. App. A10010 (citing“[p]revious studies” that concluded “measurement of6-MP metabolic levels can be used to predict clinicalefficacy and tolerance” to thiopurine drugs).2

What the Prometheus patents purport to add tothe art is a recognition that particular metabolitelevels correlate to proper drug dosages for certaingastrointestinal disorders. App., infra, 2a-3a; ’623Patent at 8:40-46, C.A. App. A10010. Those correla-tions already existed in the studied patient popula-tion; Prometheus simply looked at the data for thatpopulation to “discover” the levels. App., infra, 41a-42a; C.A. App. A12833-12836, A13330-13331.

Claim 46 of the ’623 patent, for example,describes such a correlation review process. The solestep in that process involves recognizing therelevance of certain metabolite levels (known as 6-thioguanine (6-TD) or 6-methyl-mercaptopurine (6-MMP)):

46. A method of optimizing therapeutic efficacyand reducing toxicity associated with treatmentof an immune-mediated gastrointestinal dis-order, comprising:

(a) determining the level of [6-TD] or [6-MMP] ina subject administered a drug selected from

2 See also ’623 Patent at 9:13-14, C.A. App. A10011(relevant metabolite levels “can be determined bymethods well known in the art”); C.A. App. A12698-12701, A12705-12712, A12714-12718 (scientificpapers from 1982-1990 describing tests for relevantmetabolite of thiopurine); id. at A12722-12727 (1989article discussing “acute thiopurine toxicity”); id. atA12842-12844 (conceding prior testing for thiopurinemetabolites).

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the group consisting of 6-mercaptopurine,azathioprine, [6-TD], and [6-MMP], saidsubject having said immune-mediated gastro-intestinal disorder;

wherein the level of [6-TD] less than about 230pmol per 8x108 red blood cells indicates aneed to increase the amount of said drugsubsequently administered to said subject,and

wherein the level of [6-TD] greater than about400 pmol per 8x108 red blood cells or a levelof [6-MMP] greater than about 7000 pmol per8x108 red blood cells indicates a need todecrease the amount of said drug sub-sequently administered to said subject.

C.A. App. A10018; see App., infra, 3a-5a (describingpatent claims at issue). With their technical termsstripped away, Prometheus’s claims cover a physi-cian’s observation that a test result shows ametabolite level below 230, between 230 and 400, orabove 400—i.e., his mental recognition of a naturalcorrelation between metabolite level and patientcondition following administration of a drug. SeeApp., infra, 3a.

Importantly, Prometheus’s claims do not recitewhat is to be done once the physician recognizes thecorrelation. App., infra, 38a-39a. As a result, theclaims cover and preempt all such uses. They beginand end with observation of the test results. Whatthe physician might do with that observation isirrelevant because simply thinking about the subjectsuffices to infringe the patent. As Prometheus’sexpert testified, if the physician reads an email withthe test results, it would not matter if she “crumples

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it up, throws it away, reads it, acts on it, doesn’t acton it, any assumptions you want to come up with.”C.A. App. A13557-613558; see also C.A. Supp. App.A13805-13806. The physician infringes the momentshe recognizes the correlation.

Prometheus confirmed the broad scope of itsclaims when it opposed Mayo’s argument in thedistrict court that the claims should be construed torequire that physicians actually do something withtheir knowledge before they could be deemed toinfringe—e.g., adjust a dosage level for the patient.C.A. App. A12245-12249. Prometheus successfullyargued that the physician would only have toidentify a potential need to adjust dosage and deniedthat the physician must actually adjust the dosage ordo anything else. See App., infra, 84a-86a.

The extraordinary breadth of Prometheus’spatents is made evident by Prometheus’s infringe-ment accusations against Mayo researcher Dr. Rokeael-Azhary. Dr. el-Azhary is a dermatologist andtherefore unconcerned with metabolite ranges forgastrointestinal disorders. She administered athiopurine drug to her dermatological patients to seeif she could establish a therapeutic range for skindisorders. See C.A. App. A12846. But because the labreport she received referred to the correlation rangesin Prometheus’s claims, Prometheus accused Dr. el-Azhary of infringement:

The Biochemical Genetics Laboratory atMayo Clinic Rochester sent a report of testresults to Dr. el-Azhary, or someone workingfor Dr. el-Azhary. The test results describedthe “therapeutic range” as “235-400.” TheBiochemical Genetics Laboratory at MayoClinic Rochester did not subsequently advise

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Dr. el-Azhary that the “therapeutic range”was not “235-400.”

Such information informed Dr. el-Azhary, orsomeone working for Dr. el-Azhary (and thus“indicated a need”), that the next dose ofazathioprine given to the patient should beincreased in order to be within the“therapeutic range.”

C.A. App. A12788; A12821-12822. Prometheus evenasserted infringement when Dr. el-Azhary sub-sequently received reports that did not list the“therapeutic range”—on the ground that the rangeswere then in her memory. Id. at A12853-12854 ¶ 5.

Dr. el-Azhary testified that she knew thenumbers, but that metabolite levels relevant togastrointestinal conditions were “irrelevant to [her]study” because she was researching metabolitecorrelations in dermatology, not in inflammatorybowel disease, and “there is no reason to extrapolateto dermatology.” C.A. App. A12848-12850. UnderPrometheus’s view of its patents, however, Dr. el-Azhary cannot resume her dermatological researchunless and until she rids her memory of thecorrelations that Prometheus observed in gastro-intestinal patients, regardless of how she ultimatelymay use any test results. She infringes whenever sherecognizes the correlations, no matter what else shethinks or does.

In the courts below, Prometheus attempted togloss over its accusation against Dr. el-Azhary bypointing out that it sued Mayo and not Dr. el-Azhary.But the el-Azhary episode dramatically highlightsthe broad range of medical research that Prometheushas preempted with its patents. By targeting Dr. el-

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Azhary’s thoughts, Prometheus can effectively stopher from determining appropriate ranges for her owndermatology patients, because she cannot defini-tively stop thinking about the metabolite correlationson which Prometheus’s patents are based. Anyonewho has read Prometheus’s patent claims, or anysummary of them—including readers of this petition—is similarly disabled. That Prometheus did notname Dr. el-Azhary as a defendant misses the point.If Prometheus were right that she has infringed itspatents, any owner of a patent with similar claimscould sue a physician in Dr. el-Azhary’s position forinfringement simply for thinking “forbidden”thoughts. The patent laws were never meant toimpose such intolerable consequences.

B. The District Court’s Decision Invali-dating The Patents

In 2004, Prometheus filed a patent infringementclaim against Mayo after Mayo developed andproposed to sell a test to measure metabolites inpatients treated with thiopurine drugs that useddifferent levels from those included in Prometheus’spatents. App., infra, 61a-62a. Construing Prome-theus’s patent claims in accordance with their broadlanguage, the district court granted Prometheussummary judgment on its infringement claim. Id. at86a-93a.

After the district court permitted the parties toamend their pleadings, Mayo filed a motion forsummary judgment contending that Prometheus’spatents were invalid. The court granted Mayo’smotion, at the same time denying Prometheus’smotions for summary judgment on infringement andpatent exhaustion. See App., infra, 28a-30a (describ-ing procedural history).

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In invalidating Prometheus’s patent claimsunder 35 U.S.C. § 101, the district court relied onthis Court’s case law deeming patent claims invalidif they wholly preempt all uses of a naturalphenomenon or abstract idea. App., infra, 36a-39a,42a, 48a-54a. The court started by determining thatthe Prometheus claims recite correlations betweenthiopurine drug metabolite levels and therapeuticefficacy or toxicity. Id. at 38a-39a. The court rejected,as form over substance, Prometheus’s argument thatthe claims recite “methods” rather than naturalphenomena. Looking at the steps of the claims, thecourt explained that the steps reciting “adminis-tering” a drug and “determining” metabolite levelswere mere data-gathering steps that were necessaryprecursors for reviewing the claimed correlation. Id.at 39a. In summarizing the claims, the court noted:“what the inventors claim to have discovered is thatparticular concentrations of [thiopurine metabolites]correlate with therapeutic efficacy and toxicity inpatients taking AZA drugs.” Ibid.

The court then ruled that the correlations arenatural phenomena. Rejecting Prometheus’s argu-ment that the correlations could not be naturalbecause thiopurine is a synthetic drug, the courtobserved that Prometheus’s claims are directed tothe correlation and not to the making of the drug.Prometheus’s expert had admitted that “the keytherapeutic aspect of such thiopurine drugs is thatthey are converted naturally by enzymes within thepatient’s body to form an agent that is thera-peutically active.” App., infra, 41a. Prometheus alsoadmitted that the testing and correlations alreadyexisted in a “data-base of patient’s information” thatincluded patients taking 6-MP drugs, and that thecorrelations likely still exist in the current patient

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population. Ibid. As a result, the court concluded (id.at 42a), Prometheus

did not “create” the correlation betweenthiopurine drug metabolite levels andtherapeutic efficacy and toxicity. Instead, thecorrelation results from a natural bodyprocess, which as the inventors concede, waspre-existing in the patient population, and itexists in the patient population today.

In analyzing Prometheus’s claim, the districtcourt found instructive the opinion of JusticesBreyer, Stevens, and Souter in LabCorp. The districtcourt quoted approvingly the LabCorp dissenters’explanation that the similar patent claim at issuethere failed “the requirement that it not amount to asimple natural correlation, i.e., a ‘natural phen-omenon’” (citing this Court’s precedents):

At most, respondents have simplydescribed the natural law at issue in theabstract patent language of a “process.” Butthey cannot avoid the fact that the process isno more than an instruction to read somenumbers in light of medical knowledge. Onemight, of course, reduce the “process” to aseries of steps, e.g., Step 1: gather data; Step2: read a number; Step 3: compare thenumber with the norm; Step 4: actaccordingly. But one can reduce any processto a series of steps. The question is whatthose steps embody. And here, aside from theunpatented test, they embody only thecorrelation between homocysteine and vita-min deficiency that the researchers uncov-ered. In my view, that correlation is anunpatentable “natural phenomenon,” and I

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can find nothing in [the claim] that addsanything more of significance.

LabCorp, 548 U.S. at 137-138 (citation omitted),quoted at App., infra, 43a-44a.

Finally, applying this Court’s precedents to therecord before it, the district court held that thePrometheus claims preempt a natural phenomenon.It first noted that the governing test was not a“transformation/results” test, because this Court hadutilized a preemption test in Gottshalk v. Benson,409 U.S. 63 (1972), and had invalidated a claim inParker v. Flook, 437 U.S. 584 (1978), under thepreemption rule without ever mentioning that test.App., infra, at 49a-50a. Then, applying the pre-emption rule, the court held that Prometheus’ssweeping claims improperly preempt all uses of thecorrelations. Id. at 51a-54a. That ruling followedfrom the court’s earlier determination that everyother activity described in the claims, apart fromrecognition of the correlation, is a data gatheringstep necessary to make the correlation (id. at 51a):

what the inventors claim to have discoveredis that particular concentrations of 6-TG and6-MMP correlate with therapeutic efficacyand/or toxicity in [patients] taking AZAdrugs. Because the claims cover the correla-tions themselves, it follows that the claims“wholly pre-empt” the correlations.

C. The Federal Circuit’s Decision Uphold-ing The Patents

The Federal Circuit reversed. It glossed overJustice Breyer’s LabCorp opinion in a footnote,describing it as non-binding but never dealing withits synthesis of controlling law. While noting that the

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Prometheus claims addressed different blood testsfrom those in LabCorp, the court of appeals did notcome to grips with the fact that both sets of claimspurport to cover a mental correlation betweenpatient metabolite levels and patient health.

Instead of applying this Court’s “preemption”test, as the district court had done, the FederalCircuit applied its own “machine or transformation”test from In re Bilski, 545 F.3d 943 (Fed. Cir. 2008)(en banc), cert. granted, 129 S. Ct. 2735 (2009). TheFederal Circuit began by calling its “machine ortransformation” criterion a “definitive test,” andended by declaring that it replaces the preemptionstandard:

[B]ecause the claims meet the machine-or-transformation test, they do not preempt afundamental principle.

App., infra, 24a.

Prometheus invited that ruling by insisting in itsbriefing that “a freestanding preemption inquiry isinappropriate” because “Bilski’s ‘machine or transfor-mation test is the singular test for a process claimunder § 101.’” Prometheus Reply Br. at 21 n.3 (Fed.Cir. Apr. 24, 2009) (quoting In re Ferguson, 558 F.3d1359, 1365 (Fed. Cir. 2009)). The Federal Circuitultimately focused only on Bilski and its own“machine or transformation” test—mentioning thisCourt’s decisions principally through citations to theBilski opinion. App., infra, 9a-10a, 15a, 18a. Thus,the Federal Circuit has effectively rendered thisCourt’s preemption test meaningless by making itsown “machine or transformation” test controlling.

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REASONS FOR GRANTING THE PETITION

By making its “machine or transformation” testthe definitive test for patentability under Section101, the Federal Circuit assumes that a process thatinvolves a machine or transformation cannot possiblypreempt all uses of a fundamental scientificprinciple. That ruling conflicts with this Court’sprecedents. This Court has utilized the preemptionstandard as a freestanding criterion, has foundpreemption without ever asking whether an inven-tion involves a machine or transformation, and hasdeemed the presence of a machine or a transforma-tion a mere “clue” to patentability. Like the claims inLabCorp, the Prometheus claims do not come close toescaping the preemption prohibition. The FederalCircuit’s ruling should accordingly be reversed.

I. THE FEDERAL CIRCUIT’S ELEVATION OFITS “MACHINE OR TRANSFORMATION”TEST TO THE SINGLE DETERMINANT OFPATENTABILITY CONFLICTS WITH THISCOURT’S PREEMPTION STANDARD.

A. The Court has long invalidated patentclaims that attempt to preempt all usesof a natural phenomenon.

Although Section 101 is expansive in its reach—covering “anything under the sun that is made byman,” Diamond v. Chakrabarty, 447 U.S. 303, 309(1980)—it also is subject to important limits. Inparticular, a patent claim cannot preempt, eitherdirectly or by practical effect, a law of nature,natural phenomenon, or abstract scientific idea. AsChakrabarty observed:

[A] new mineral discovered in the earth or anew plant found in the wild is not patentable

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subject matter. Likewise, Einstein could notpatent his celebrated law that E=mc2; norcould Newton have patented the law ofgravity. Such discoveries are ‘manifestationsof * * * nature, free to all men and reservedexclusively to none.’

Id. at 309 (quoting Funk Bros. Seed Co. v. KaloInoculant Co., 333 U.S. 127, 130 (1948)). As theCourt has also noted, “[p]henomena of nature,though just discovered, mental processes, andabstract intellectual concepts are not patentable, asthey are the basic tools of scientific and technologicalwork.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972).

This exception to patentability applies not only toa patent claim that is aimed directly at a naturalphenomenon, but also to one whose “practical effectwould be a patent on the [phenomenon] itself,”because such a claim “wholly pre-empt[s]” all uses ofthe natural phenomenon. Benson, 409 U.S. at 71-72.Thus, where a claim recites a law of nature orbiological principle, a court must look to whether theclaim seeks protection for the phenomenon “in theabstract” or instead implements the phenomenon “ina structure or process which, when considered as awhole, is performing a function which the patentlaws were designed to protect.” Diamond v. Diehr,450 U.S. 175, 191 (1981).

B. Prometheus’s claims are invalid becausethey preempt all uses of the naturalcorrelation between patient metabolitelevels and patient health.

The Prometheus claims, like the LabCorp claims,recite a natural phenomenon—the correlation be-tween certain metabolite levels and patient health.

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That correlation is dictated by natural enzymaticactivity inside the human body. As Prometheus’sown expert admitted, the drugs are “convertednaturally by enzymes within the patient’s body” intometabolites, as the district court found. The FederalCircuit did not disturb that finding by the districtcourt.

The Prometheus claims preempt all substantialuses of the correlations. In particular, the claims endwith the step of recognizing the correlation, and thuscover anything that a physician might do with herknowledge of the correlation. Prometheus’s expertconfirmed the preemptive effect of the claims bytestifying that a physician who receives test resultsthat identify the claimed ranges will infringeregardless of what she does with the information—even if she crumples up the test result and throws itaway, and regardless of whether or not she acts uponit. C.A. App. A13557-613558; see also C.A. Supp.App. A13805-13806.

The preemptive impact of Prometheus’s claims isparticularly severe because they are centered onhuman thought that involves, in any medicalcontext, metabolite ranges that Prometheus observedin patients who took gastrointestinal drugs. Thus,dermatologist Dr. el-Azhary cannot stop thinkingabout Prometheus’s ranges now that she knows ofthem, even if her goal in reviewing a patient’s testresults is to find entirely different numbers relatingonly to dermatology. As a result, Prometheus hasobtained a monopoly in a very broad field of medicalpractice. The preemptive scope of the Prometheusclaims is unprecedented. It constitutes an embargoon research and analysis essential to the develop-ment of medical knowledge and patient care.

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This Court’s decisions in Benson, Flook, andDiehr explain the governing preemption standard. InFlook and Benson, the claims were invalid becausethey recited a computation but not what was to bedone with the computation, thereby covering all itsuses. In Diehr, the claim recited both a computationof an algorithm and a real-world physical action to beperformed with the computation, thus leaving openthe possibility that others could make noninfringinguses of the computation. Because it was so limited,there was no preemption. The claims in Bensonrecited a computation for converting numbers fromone form to another, but did not recite what was tobe done with the numbers once they were converted.Hence, the patent covered all such uses of the ideaand would wholly preempt the underlyingmathematical formula. 409 U.S. at 71-72. In a likemanner, the claims in Flook recited a process forupdating an alarm limit for use in a chemicalprocess, but never recited what was to be done withthe computation even though the claims did recitesome “post-solution activity.” 437 U.S. at 590.Because the claims covered all uses, they, like theclaims in Benson, were held invalid.

By contrast, the claims in Diehr, which reciteduse of the Arrhenius equation, also recited aparticular application of the equation: using theoutput of the equation to determine when to open orclose an injection mold. In distinguishing thatsituation from Benson and Flook, the Courtexplained (450 U.S. at 187) that

respondents here do not seek to patent amathematical formula. Instead, they seekpatent protection for a process of curingsynthetic rubber. Their process admittedly

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employs a well-known mathematicalequation, but they do not seek to pre-emptthe use of that equation. Rather, they seekonly to foreclose from others the use of thatequation in conjunction with all of the othersteps in their claimed process.

Prometheus’s claims are like those in Benson andFlook and unlike those in Diehr. Claim 46, quotedabove, involves nothing more than a physician’srecognition of a natural correlation that is part andparcel of a patient’s own natural metabolic processes.The claim is not limited to a particular real-worlduse of that recognition, such as requiring that thephysician actually change the dosage after recogni-zing the correlation. Rather, the claim preempts allpossible uses of the correlation and thus effectivelymonopolizes the natural correlation itself.

Prometheus’s claims are invalid for the reasonsset forth in the opinion of Justices Breyer, Stevens,and Souter in LabCorp. In LabCorp, the claims weredirected to a method of “correlating” a blood homo-cysteine level with a deficiency in folate, just like thecorrelation between metabolites and patient condi-tion in the Prometheus claims. Hence, “[t]here can belittle doubt that the correlation [is] a ‘naturalphenomenon.’” 548 U.S. at 135. Like the claims inLabCorp, Prometheus’s claims simply characterizethe use of the correlation as a process, which wasplainly insufficient in LabCorp:

At most, respondents have simply describedthe natural law at issue in the abstractpatent language of a “process.” But theycannot avoid the fact that the process is nomore than an instruction to read somenumbers in light of medical knowledge. * * *

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[H]ere, aside from the unpatented test, [thesteps in the claim] embody only the correla-tion between homocysteine and vitamindeficiency that the researchers uncovered. Inmy view, that correlation is an unpatentable“natural phenomenon,” and I can findnothing in [the claim] that adds anythingmore of significance.

Id. at 137-138. Prometheus’s claims fail for the samereason.

Prometheus’s central argument in the courtsbelow was that thiopurine is a man-made, notnatural, drug (whereas the drug in LabCorp wasnaturally occurring). But as the district courtrecognized, Prometheus’s claims are directed to thecorrelation and not the drug itself (which Prome-theus did not invent). And that correlation resultsfrom the body’s natural metabolism of the drug. Inshort, Prometheus cannot take advantage of a drugthat was invented by someone else, when its claimsare exclusively directed to observing the humanbody’s process of metabolizing the drug—a processthat occurs naturally in the human body.

Granting patent protection here simply becausePrometheus used a man-made drug would beinconsistent with this Court’s invalidation of thepatent claims in Funk Bros. There, the inventordiscovered that certain bacteria could be isolated,mixed together so as not to inhibit each other’sproperties, and thereby serve as a crop inoculant.333 U.S. at 130. The Court held the claims invalidbecause the inventor did not “create” the “state ofinhibition or of non-inhibition in the bacteria,” butinstead “[t]heir qualities are the work of nature.”Ibid. Of course the claimed combination of bacteria

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was man-made. But the inventor had not created thenatural phenomenon that was central to theinvention. Likewise, Prometheus did not “create” anycorrelation between metabolite levels and drugefficacy or toxicity, because those correlations werepre-existing in the tested patients, have beenobserved and analyzed by physicians in theirpatients for decades, and exist today with or withoutPrometheus’s patents.

In short, the Prometheus patent claims preempta broad field of scientific thought and research. Theyseek to monopolize a scientific principle in a mannerthat is forbidden by this Court’s patent preemptionrulings. The Federal Circuit’s decision conflicts withthose rulings and should be reversed.

C. The Federal Circuit improperly appliedits “machine or transformation” test inplace of this Court’s preemptionstandard.

The fundamental error in the Federal Circuit’sresolution of this case was its replacement of thisCourt’s “preemption” standard with its own “machineor transformation” test. As shown above, this rulingis at odds with settled precedent of this Court. Inaddition, the elevation of the rigid “machine ortransformation” test to conclusive status is erroneousand exceptionally harmful.

First, although the Federal Circuit in Bilskiclaimed to find support for its test in this Court’sdecisions in Benson, Diehr, Flook, and Cochrane v.Deener, 94 U.S. 780 (1876), those opinions do not saythat “machine or transformation” is a dispositive testfor patentability or a substitute for the preemptionstandard. For example, the portion of Benson cited

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by the Federal Circuit simply says that a trans-formation or reduction of an article to a differentthing is “the clue” to patentability of a method claimthat does not involve a particular machine. 409 U.S.at 70. A clue is a guide, not a definitive test.

In any event, the Prometheus claims do notresult in any transformation. The only transforma-tion cited by the Federal Circuit was a naturaltransformation that had already occurred in thepatient population that Prometheus studied before iteven looked at the test results. The transformationenvisioned by Benson and other cases is atransformation that makes particular use of thenatural phenomenon, and thus prevents the claimfrom preempting all possible uses. Likewise, theclaims in Diehr were found patentable, not because aphysical transformation was associated with them,but because the claims were limited to a narrow andparticular use of the Ahhrenius equation—openingand closing a plastic mold. 450 U.S. at 187.

The Federal Circuit’s decision draws even lesssupport from the other two cases on which it relied inBilski—Flook and Cochrane—because those casesmake no mention of such a test. The Flook claimsinvolved calculations performed using a computer (amachine) and included a transformation of an “alarmlimit” that signaled the presence of abnormalconditions during catalytic conversion. 437 U.S. at585-586. The Court nevertheless found the claimsinvalid because this transformation was insignifi-cant “post-solution” activity that did not alter thefact that the claim was directed at a “mathematicalformula” for updating alarm limits. Id. at 593-595.While the Court observed in a footnote that an“argument can be made” that the Court has affirmed

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process claims only when the process “either was tiedto a particular apparatus” or operated to changematerials to a “different state or thing” (id. at 588n.9), Flook did not adopt such a position. Even thatpossible “argument” made “machine or transforma-tion” a minimum requirement, not a definitive testfor patentability.

Likewise, in Cochrane, the Court simply notedthat a process “is a mode of treatment of certainmaterials to produce a given result,” and “an act, or aseries of acts, performed upon the subject-matter tobe transformed and reduced to a different state orthing.” 94 U.S. at 788. It did not identify either“machine” or “transformation” as a test, let alone thetest, for patentability. By their omission of any“machine” or “transformation” analysis, these twocases confirm that “machine or transformation” isnot the definitive standard for patentability underSection 101.

Shutting its eyes to this Court’s preemptionstandard, the Federal Circuit observed that giving adrug to a patient was “‘central to the purposes of theclaimed process.’” App., infra, at 10a; see id. at 20a.But the court overlooked the fact that giving thedrug was simply a preparatory data-gathering stepfor the ultimate correlation and did not limit the useof the correlation in any manner. The court alsomisperceived the relevance of any “transformation.”If the transformation limits the claim to a particularreal-world use of the fundamental principle, it can besupportive of patentability. But if it is merely apreparatory data-gathering step—leaving the rest ofthe claim open to preempt all uses of the principle—it does not make an otherwise unpatentable claimpatentable. Thus, whether or not a patient receives a

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thiopurine drug (a drug not invented by Prome-theus), none of Prometheus’s claims is limited in anymanner: they cover anything done with knowledge ofthe natural correlation.

In the end, the “machine or transformation” testappears to be another effort by the Federal Circuit tofashion an inflexible standard that is unmoored fromCongress’s purposes in enacting the patent laws.This Court repeatedly has rebuffed such interpreta-tions in recent years. For example, in KSR Int’l Co. v.Teleflex, Inc., 550 U.S. 398, 418 (2007), the Courtfaulted the Federal Circuit for establishing aninflexible “teaching, suggestion or motivation tocombine” standard that did not comport with theunderlying rationale set forth in Graham v. JohnDeere Co., 383 U.S. 1 (1962), and other precedents. InMedimmune, Inc. v. Genentech, Inc., 549 U.S. 118(2007), the Court was critical of the Federal Circuitfor adopting an inflexible rule for declaratoryjudgment jurisdiction, where that rule was unmooredfrom the underlying “case or controversy” require-ment. And in eBay Inc. v. MercExchange, L.L.C., 547U.S. 388 (2006), the Court faulted the FederalCircuit for applying an inflexible injunction standardthat did not address the full range of underlyingequitable considerations. The Federal Circuit’sadoption of a rigid “machine or transformation”standard here, which allows Prometheus to preempta broad field of scientific thought and research, isequally indefensible.

II. CERTIORARI SHOULD BE GRANTED TORESOLVE THE IMPORTANT QUESTIONLEFT UNRESOLVED IN LABCORP.

The Court should grant review rather than holdthe petition for Bilski. As the government empha-

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sized in Bilski, that case turns on whether BernardBilski’s invention is the sort of “technology” thatshould properly be protected by a patent. E.g., U.S.Br. in Bilski, No. 08-964, at 8 (issue in Bilski iswhether “methods of organizing human activity thatare untethered to technology” are “technological andindustrial processes” eligible for protection underSection 101). The resolution of that case will notdecide the independent question raised here—whether an invention preempts a scientific idea bycovering all uses.

This Court has already found the issue presentedhere to be certworthy in LabCorp. This case is anappropriate vehicle to resolve the important issueleft undecided there for lack of issue preservation.The Prometheus invention is easy to understand andcentered on a plain natural phenomenon. TheSection 101 issue was the only issue raised onappeal, and it was addressed directly and extensivelyby the Federal Circuit and the district court. Andbecause the Federal Circuit has exclusive jurisdic-tion over patent appeals from district courts (28U.S.C. § 1295), erroneous decisions such as this onehave immediate nationwide impact. Accordingly, thisCourt often grants review of Federal Circuit rulingsbased on the importance of the issue presented to theinterpretation and application of the patent laws.E.g., Merck KGaA v. Integra Lifesciences I, Ltd., 545U.S. 193 (2005). Such review is especially warrantedhere because the Federal Circuit’s analytical error isfundamental and will be repeated if not corrected bythis Court.

Furthermore, the question presented is one ofextraordinary public importance at the heart of thepatent laws. The critical need for this Court to

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resolve that issue now is evidenced by the extensiveamicus participation both in LabCorp and in theFederal Circuit in this case. Many amici stressedthat patents like Prometheus’s impede improve-ments in healthcare, drive up costs, and freezeinnovation, as the dissenting Justices in LabCorpalso recognized (548 U.S. at 138):

[S]pecial public interest considerationsreinforce my view that we should decide thiscase. To fail to do so threatens to leave themedical profession subject to the restrictionsimposed by this individual patent and othersof its kind. Those restrictions may inhibitdoctors from using their best medicaljudgment; they may force doctors to spendunnecessary time and energy to enter intolicense agreements; they may divertresources from the medical task of healthcare to the legal task of searching patent filesfor similar simple correlations; they mayraise the cost of health care while inhibitingits effective delivery.

These adverse consequences are profound giventhe sweep of the Federal Circuit’s ruling and extendfar beyond gastrointestinal disorders. If Prometheuscan obtain a patent on correlations between drugadministration and the resulting biological reactionsin the human body, and prevent medical researchersand providers from thinking about those correlationsin different ways, a host of medical entrepreneurswill claim patent monopolies on blood tests with thesame preclusive consequences. A patent claimantcould seek, for example, to monopolize the correla-tion between administration of anticoagulant drugsand chemical reactions in the blood, asserting that

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these reactions are “man-made” phenomena, andthereby preclude improvements in this commonplaceand essential form of medical care.

Therapeutic drug monitoring is fundamental tosafely and effectively treating a variety of patientdisorders with medication. Mayo, and physiciansthroughout the world, routinely measure metabolitelevels in patients being treated with an array ofdrugs, including those for the treatment of epilepsy,heart arrhythmias, and depression. Therapeuticmonitoring is also central to medicines used in thetreatment of organ transplant and cancer patients.Improvements in the administration of all these life-saving drugs would be curtailed if patent claimantscould assert a monopoly over every use of metaboliteor other therapeutic correlations.

In this very case, Mayo sought to adjust themetabolite reference range deemed relevant byPrometheus to achieve more accurate results andimproved patient care. App., infra, at 61a; MayoMem. in Support of Summary Judgment, filed Mar.17, 2005, at 5-6 (Dkt. No. 15). But Prometheusblocked that innovation by asserting that it infringedPrometheus’s exclusive right to specify relevantbiological correlations.

The harmful impact of overly broad intellectualproperty protection on innovation is also of moregeneral concern for the U.S. economy. Academiccommentary confirms that allowing patents topreempt important fields, like medical diagnosis, bymonopolizing scientific laws, would greatly increasecosts and retard innovation. See M. Boldrin & D.Levine, AGAINST INTELLECTUAL MONOPOLY 73-77, 89-92, 184-187, 214-218, 238, 246 (2009) (describingdramatic increase in patent grants over last decade

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resulting in a “patent thicket” harmful toinnovation); L. Lessig, THE FUTURE OF IDEAS 205-217(2001) (describing negative impact of broad patentprotection on innovation; “we should be mostconcerned when existing interests use the legalsystem to protect themselves against innovation”);W. Landes & R. Posner, THE ECONOMIC STRUCTURE

OF INTELLECTUAL PROPERTY LAW 305-306 (2003)(patent monopolies on “scientific principles” threaten“enormous potential for rent seeking” and “enormoustransaction costs that would be imposed on would-beusers”); R. Merges & R. Nelson, On the ComplexEconomics of Patent Scope, 90 COLUM. L. REV. 839,915 (1990) (“[T]he real threat of a patent like thisstems from the industry’s close ties to science. * * *The Patent Office and courts should not permit theover-privatization of the scientific knowledge thatmakes the industry possible”); L. Branstetter, DoStronger Patents Induce More Local Innovation?, 7 J.INT’L ECON. L. 359, 369 (2004) (“well-structuredresearch projects conducted by competent scholars”have “failed to find” innovation benefits fromexpanded patent monopolies); A. Torrance & B.Tomlinson, Patents and the Regress of Useful Arts, 10COLUM. SCI. & TECH. L. REV. 130, 138, 162-167 (2009)(collecting economic research showing lack ofstimulus to innovation from broad patent grants).

At a minimum, and especially at this time ofparamount national concern over health care costsand quality, this research shows “that a heavyburden of persuasion should be placed upon thosewho would extend such protection.” S. Breyer, TheUneasy Case for Copyright, 84 HARV. L. REV. 281,322-323 (1970) (citing research in patent andcopyright fields). Prometheus has offered no such

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justification for its sweeping monopoly on medicalthought and research.

Beyond this, the decision below cannot bereconciled with the ethical duties of physicians. Asexplained in amicus briefs filed in the FederalCircuit by the American Medical Association andother medical organizations, patent protection ofPrometheus’s claims conflicts with ethical standardsthat require physicians to spread knowledge—andimprove diagnostic criteria—for the benefit ofmankind.

The Federal Circuit’s decision also posesexceptional threats to First Amendment freedoms.Throughout our Nation’s history, the freedom tothink—to consider what one has seen, to reachmental conclusions based on those observations, andto change one’s future plans in light of thoseconclusions—has been deemed sacrosanct. Reflectingthat tradition, this court held in Ashcroft v. FreeSpeech Coalition, 535 U.S. 234, 253 (2002), thatspeech is generally protected from governmentrestriction because “[t]he right to think is thebeginning of freedom, and speech must be protectedfrom the government because speech is thebeginning of thought.” Federal legislation, like thepatent laws, must be construed to avoid conflict withFirst Amendment freedoms whenever possible. See,e.g., New York v. Ferber, 458 U.S. 747, 769 n.24(1982); ACLU Am. Br. in Bilski, No. 2007-1130 (Fed.Cir. Apr. 3, 2008), at 5-7, 14, available at http://www.aclu.org/pdfs/freespeech/in_re_bilski_aclu_amicus.pdf

(a patent like that at issue in LabCorp amounts “to apatent on pure thought or pure speech”; courts“should interpret patent law doctrines * * * so as to

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avoid difficult application of First Amendmentdoctrines”).

Yet the decision below would make mere thoughtactionable under patent law and threaten sanctionsincluding actual and treble damages. 35 U.S.C.§ 284. Simply drawing a mental conclusion becomes,under the Federal Circuit’s view, patent infringe-ment, even without any further act. The infringe-ment is complete when a doctor has recognized acorrelation between the patient’s metabolite levelsand the patient’s status, regardless of what thedoctor may do based on such recognition. This cannotbe the legal rule in a Nation committed to the FirstAmendment and to the tradition of freedom ofthought.

At bottom, the Federal Circuit’s ruling autho-rizes patents over the mere observation of naturalphenomena. That ruling flouts this Court’s prece-dents and the fundamental purpose of the patentlaws. And it puts a stranglehold on innovation andprogress in the vital field of medical diagnosis.

CONCLUSION

The petition for a writ of certiorari should begranted to resolve the issues left undecided inLabCorp. At a minimum, the petition should begranted, the decision below vacated, and the caseremanded for reconsideration in light of this Court’sdecision in Bilski.

Respectfully submitted.

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JONATHAN E. SINGER

JOHN A. DRAGSETH

Fish & Richardson P.C.3200 RBC Plaza60 South 6th StreetMinneapolis, MN 55402(612) 335-5070

EUGENE VOLOKH

405 Hilgard AvenueLos Angeles, CA 90095

STEPHEN M. SHAPIRO

Counsel of RecordTIMOTHY S. BISHOP

JEFFREY W. SARLES

Mayer Brown LLP71 South Wacker DriveChicago, IL 60606(312) 782-0600

Counsel for Petitioners

OCTOBER 2009