Amicus Curiae Brief — Laboratory Corp. of America Holdings v. Metabolite Laboratories, Inc.

Sujc:3:* Lost, UR

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Q DEC 22 2005

No. 04-607 vides

IN THE

Supreme Court Of The Gnited States _

LABORATORY CORPORATION OF AMERICA HOLDINGS, DBA

LABCORP, PETITIONER

Vv.

METABOLITE LABORATORIES, INC., ET AL., RESPONDENTS

On Wnt of Certiorari to the United States Court of Appeals

for the Federal Circuit

BRIEF OF AMICUS CURIAE PEOPLE’S MEDICAL

SOCIETY IN SUPPORT OF PETITIONER

LORI B. ANDREWS FRANCIS C. J. PIZZULLI

Counsel of Record 718 Wilshire Boulevard

DEBRA GREENFIELD Santa Monica, CA 90401

CLEMENTS RIPLEY Tel: 310-451-8020

Chicago-Kent College of Law

565 West Adams Street

Chicago, IL 60611

Tel: 312-906-5359

December 22, 2005

Re a ETS

Y

QUESTION PRESENTED

Whether a method patent setting forth an indefinite,

undescribed, and non-enabling step directing a party simply

to "correlat[e}" test results can validly claim a monopoly over

a basic scientific relationship used in medical treatment such

that any doctor necessarily infringes the patent merely by

thinking about the relationship after looking at a test result.

TABLE OF CONTENTS

SP COINS SMITE TIED csccecnesnccsnecececessnunsescntonsentennsnns i

ee Oe Ge itiseccctsniccssecanstininttinnichintamtiotinte il

TABLE | SESE onan > iV

STATEMENT OF INTEREST OF AMICUS

CURIAE PEOPLE’S MEDICAL SOCIETY.................. l

SUMMARY OF ARGUMENT...........:ccssesscssseessssesesseees 4

UNITES <iebiositncansisdhciiiininiavasitiiiitinaepiclnaainibapsiaaeiaiiiaadias 5

ie NINN <sileccischiciescieteciiaeiadeiimcthanblahiguinhaiponiaiinaed 5

II. Claim 13 of the ‘658 Patent Is Not Patentable

Subject Matter and Should be Held Invalid. ............ 7

A. Claim 13 of the ‘658 Patent Is Not a

“Discovery” Within the Meaning of Article I,

Section 8, Clause 8 of the U.S. Constitution. .....7

B. Claim 13 of the ‘658 Patent Operates as an

Unpatentable “Law of Nature” Under 35

Se Ue Wes cenciincictibtiisctensidisibiabiapaiiiinittinsiineiaies 9

C. Claim 13 of the ‘658 Patent Is Distinguishable

From an Allowable Patent Claim Which

Merely Incorporates a Law of Nature in a.

Larger, Patentable Process. ..................00vsseerseess 12

III. Patent Protection for Claim 13 of the ‘658 Patent

Chills the Exercise of First Amendment Rights....... 17

A. Claim 13 of the ‘658 Patent Chills the Exercise

of Freedom of Thought..........-ccccccccsscesessesseeeeeees 18

B. Claim 13 of the ‘658 Patent Chills the Exercise

OF POUREIE OF BBGII. ses. cccccccncecseessccssescocecenes 19

IV. Allowing Claim 13 of the ‘658 Patent to Stand as

Valid Would Have Untenable Policy Implications ..21

A. Upholding Claim 13 of the ‘658 Patent Would

D.

zg.

Have a Negative Impact on Health Care in the

_ | ERENT SET Ore VRE Oe OD 21

. Upholding Claim 13 of the ‘658 Patent Would

Have a Negative Impact on the Dissemination

of Medically Relevant Information.................... 23

Upholding Claim 13 Would Have a Negative

RII, 1s sisinsin/siacsctednetaindiabdieaieiabesadiiin 24

Upholding Claim 13 Would Deter People

From Participating in Medical Research. .......... 25

Adherence to the Law of Nature Doctrine Will

I, Seccilitintseiiiadechitiiencatesenticaiatihad 26

EY istericihinriteiciseceiatseesetiaisniaanciiipesianenisticiasesi 27

-iV-

TABLE OF AUTHORITIES

United States Constitution

Sa GT, TE Tha scrisicceiuecsctnnnedisiiiedatabisscietieaamaiaa een 17

U.S. Const., art. I, § 8, OG cccescconesssccovesonevesomnes 3,4,7,9

Statutes

SF Saualin 1 PT cedpcsitiiecnsdésssiibendbasiaeisteisiiniam mina aaa 21

Be Cs WF Si sv nsecscsncticdabdadessiineeabeaaaeen 4,9,12

Be Wiss FB ins scivesic docesesteecbanacs dies keno beac 13

Be Wace EOF incninincinevcnieiatinieecbataiiiiiee 22

Regulations

Internal Revenue Code § S01 ........ss..sscessccsscosegssvesssvesseoees l

United States Patent and Trademark Office, Official

Gazette Notices, iNovember 22, 2005, Section II............... 5

U. S. Supreme Court Decisions

Bonito Boats, Inc. v. Thunder Craft Boats, Inc., 489

SJ DEG GIDID cccnrcscevimsinipsesintientennsicodunicsamiiaasdauann 17

Cochrane v. Deener, 94 U.S. 780 (1877) .....cccccccccccececeeeeee 12

Diamond v. Chakrabarty, 447 U.S. 303 (1980).......... 10, 26

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

sneeesésasteldtneininliodesinntiadebadieenadaademmaaaaaiae 4,9, 10, 12, 15, 16, 27

Funk Bros. Seed Co. v. Kalo Inoculant Co., 333 U.S.

SBF COREE ssecsscsesendeiastinntasiinmedeenate nn 10

-V-

Globe Newspaper Co. v. Superior Court, 457 U.S. 596

areata cinceeecerensesnnntenenenccentsens 18

Gottschalk v. Benson, 409 U.S. 63 (1972)....4, 10, 12, 14, 17

Graham v. John Deere Co., 383 U.S. 1 (1966)........... 24, 26

_ Griswold v. Connecticut, 381 U.S. 479 (1965) ........c0cc0000+. 21

Le Roy v. Tatham, 55 U.S. (14 How.) 156 (1853).............. 10

O'Reilly v. Morse, 56 U.S. (15 How.) 62 (1853)............ 10, 11

Parker v. Flook, 437 U. S. 584 (1978)...........4, 10, 13, 15, 17

Palko v. Connecticut, 302 U.S. 319 (1937) voccccccccccccccceeeee. 18

Richmond Newspapers v. Virginia, 448 U.S. 555 (1980)

ansaanasaieinnaaneancennbteintitnnadeneetntnecnsntdeceecienseentennessesentesensensases 18

Wooley v. Maynard, 430 U.S. 705 (1977) .o.ccccccccccccecceseeeee 18

Other Court Decisions

General Electric Co. v. DeForest Radio Co., 28 F.2d

641 (3rd Cir. 1928), cert. denied 278 U.S. 656 (1929)...... 10

In re Cruciferous Sprout Litigation, 301 F.3d 1343

ES ee 10

Madey v. Duke Univ., 307 F.3d 1351 ....000000000 0 cccececeeee 21

Metabolite Labs., Inc. v. Lab. Corp. of Am. Holdings,

370 F.3d 1354 (2004) ....... 6, 12, 14, 17, 18, 19, 20, 22, 23

-Vi-

Moore v. Regents of the University of the University of

California, 51 Cal.3d 120, 793 P.2d 479 (1990) 0.000.000... 25

International Law \

Agreement on Trade-Related Aspects of Intellectual

Property Rights (TRIPS Agreement), Dec. 15, 1993, 33

eens CIT niteicicnesiadetinecttindiantaditinamsannsinisdndl 22, 23

European Patent Convention, Article 52(2) (1998)............ 8

Gen’! Secretariat of the Council of Eur. Communities,

Records of the Luxembourg Conference on the

Community Patent 1973, art. 31(B) oo... cece ceeeeeeee 21

Miscellaneous

American Medical Association, Council on Ethical and

Judicial Affairs, Code of Medical Ethics: Current

Opinions with Annotations, Section 2.08, Commercial

Use of Human Tissue (Chicago: AMA, 2000) .................. 25

Lon B. Andrews, Genes and Patent Policy: Rethinking

Intellectual Property Rights, 3 Nature Reviews

ETA a ene ee 3

William R. Cornish, Experimental Use of Patented

Inventions in European Community States, 29 Int’|

Rev. Indus. Prop. & Copyright L. 735 (1998) ...0000..000000.. 21

Linda J. Demaine & Aaron Xavier Fellmeth,

Reinventing the Double Helix: A Novel and Nonobvious

Reconceptualization of the Biotechnology Patent, 55

Es SET aS: 8

-Vil-

Charles Inlander, The Men's Health and Wellness ~

Encyclopedia (MacMillan Publishing Co., 1998) ............. ]

~ Charles Inlander et al., Medicine on Trial (Prentice

cl PE cE ENS aN oa 1

Charles Inlander et al., The People's Medical Society

Health Desk Reference (Hyperion Books, 1996) .............. 2

E. Joosten et al., Cobalamin Absorption and Serum

Homocysteine and Methylmalonic Acid in Elderly

Subjects with Low Serum Cobalamin, 51 Eur. J.

Se CIID dciccinsuinihinsheesnaetiiibicindinieniahiiclinsinieiadaieaiaiint 20

E. Joosten et al., /s Metabolic Evidence for Vitamin B-

12 and Folate Deficiency More Frequent in Elderly

Patients with Alzheimer's Disease?, 52 J. Gerontol A.

Biol. Sci. Med. Sci. 2, M76-9 (1997) ......ccccccccescseeceeeeereeee 20

Jensen M. Krogh et al., Folate and Homocysteine

Status and Haemolysis in Patients Treated with

Sulphasalazine for Arthritis, 56 Scan. J. Clin. Lab.

NL ee eR TL 20

A. M. Kuzminski et al., Effective Treaiment of

Cobalamin Deficiency with Oral Cobalamin, 92 Blood

SUI MED ceseeasteyiicenabeiniaieemsicitimainlaeiiniatihiccahatadaad tat tala 20

Laboratory Corp. of Am. Holdings v. Metabolite Labs.,

Inc, 73 U.S.L.W. 3512 (U.S. Feb. 28, 2005) oo... eee 6

J. Lindenbaum et al., Prevalence of Cobalamin

Deficiency in the Framingham Elderly Population, 60

GRD, Gs Gs Dee BO GI cecrcrseccccecncctnsinensenesiitnanisaittcntatens 20

-Vill-

Thomas K. McBride, Jr., Patent Practice in London -

Local Internationalism: How Patent Law Magnifies the

Relationship of the United Kingdom with Europe, the

United States and the Rest of the World, 12 Loy. U.

Chi. Int’l L. Rev. 31 (2004-2005)

J. Metz et al., The Significance of Subnormal Serum

Vitamin B12 Concentration in Older People: A Case

Control Study, 44 J. Am. Geriatr. Soc. 11 (1996) .............

S.E. Miner et al., Clinical Chemistry and Molecular

Biology of Homocysteine Metabolism: An Update, 30

ee SIA SPURNED vnsteintititihinsntinninsiscinnieaatinandtnalatcen tics

Ellen Moyer, Vitamins & Minerals: Questions You

Have... Answers You Need (People’s Medical Society,

SPITITTT wsctectinageteteintiinciaggieteiianieieiaadinieein times ines Taitaantini aia

Janice M. Mueller, The Evanescent Experimental Use

Exemption from the United States Patent Infringement

Liability: Implications for Non Profit Research and

Development, 56 Baylor L. Rev. 917 (2004) .0..........cccc000.

Nationa! Institute of Health, Abour NIH, (last updated

on December 19, 2005) <http://www.nih.gov/about/> ......

H. Ono et al. Plasma Total Homocysteine

Concentrations in Epileptic Patients Taking

Anticonvulsants, 46 Metabolism 8 (1997) ....0000000000....000...

People’s Medical Society, About the Society, (last

updated on 11/25/2002) available al

<http://peoplesmed.org/abutmenu.html> 2...

-1X-

D.G. Savage et al., Sensitivity of Serum Methylmalonic

Acid and Total Homocysteine Determinations for

Diagnosing Cobalamin and Folate Deficiencies, 96

SS SREY SP ITED catinnibarnenimenisiaiaiainbaneepintinananiniel 20

S.P. Stabler et al., Elevation of Total Homocysteine in

the Serum of Patients with Cobalamin or Folate

Deficiency Detected by Capillary Gas Chromography-

Mass Spectrometry, 81 J. Clin. Invest. 2 (1988) ............ 3, 20

Katherine J. Strandburg, What Does the Public Get?

Experimental Use and the Patent Bargain, 2004 Wis.

Sis SRE SUS GUIITED - ictnentdennianiitetiiaeaiandiisincpsitntnptiatiniaiciaialiiladlinienls 21

A. E. Sumner et al., Elevated Methylmalonic Acid and

Total Homocysteine Levels Show High Prevalence of

Vitamin B; Deficiency After Gastric Surgery, 124 Ann.

LSE SPEND setscsnccvincsesiinntenstrentiapeiinteimmiintapessis 20

Laurence Tribe, American Conninsional Law § 15-7.

|) SE eee sinbiibiiailaisapaniatiisitaieiihies 18

Albert A. Walker, Text-Book of the Patent Laws of the

United States of America (L.K. Strouse & Co., 2d ed.

Ap

STATEMENT OF INTEREST OF AMICUS CURIAE

PEOPLE’S MEDICAL SOCIETY’

Amicus Curiae People’s Medical Society, an Internal

Revenue Code Section 501(c)(3) non-profit organization, is

the largest patients’ advocacy group in the United States and

iS a recognized authority on health care issues. Its mission is

to enhance the availability of health care information to

consumers and to encourage the health care system to be

more responsive to consumers. The People’s Medical

Society is regularly consulted by government agencies,

health care institutions, and companies designing health care

products and pharmaceuticals for insights into the patients’

perspective. The Society has served in an advisory capacity

to the Health Care Financing Administration of the Federal

Department of Health and Human Services on Medicare

issues, and its current president, Charles Inlander, is a

member of the Medical Error and Drug Safety Committee of

the National Academy of Sciences, Institute of Medicine. As

President of the People’s Medical Society, Mr. Inlander has

also served as a health commentator for National Public

Radio in over 250 broadcast segments.

Since its inception in 1983, the People’s Medical Society

has released over 100 books, as well as hundreds of articles,

fact sheets, and newsletters pertaining to the diagnosis and

treatment of medical conditions. Over 7,000,000 copies of

its books have been sold; the value of the medical

information in these books is attested to by the honors these

books have been accorded.’ These publications further the

' Pursuant to S. Ct. R. 37.6, People’s Medical Society states that

neither petitioner's nor respondents’ has authored any portion of this

brief. No financial contribution was made for preparation of this brief by

anyone other than Amicus and its counsel. By letters filed with the Clerk

of the Court, the parties have consented to the filing of this brief.

* For example, Charles Inlander et al., Medicine on Trial (Prentice

Hall, 1988) was honored as Book of the Year by the American Nursing

Association's American Nursing Journal. Charles Inlander, The Men's

_%

organization’s pledge “to put previously unavailable

information into the hands of ordinary people so that they can

make informed decisions about their own health care” and to

“publish infarmation designed to make every American a

smart health care consumer.”

The activities of the People’s Medical Society are

designed to benefit patients by enhancing medical care,

medical information, and medical research. If claim 13 of

U.S. Patent No. 4,940,658 (the ‘658 patent) is upheld, each

of these important activities will suffer. Moreover, if claim

13 is upheld, the charitable purpose of the People’s Medical

Society itself will be thwarted. The People’s Medical

Society could be construed to have done precisely what the

Federal Circuit held actionable in this case. In its book,

Vitamins & Minerals: Questions You Have... Answers You

Need (1993), the People’s Medical Society disclosed that

homocysteine levels were related to vitamin deficiency.‘

The unique voice of the People’s Medical Society is

particularly relevant in a patent case. In the United States,

unlike Europe, there is no general procedure for third parties

representing consumers to voice concerns at the time the U.S.

Patent and Trademark Office is considering issuing a patent.

Generally, the only entities that can challenge patents in

litigation are entities that are themselves infringing the

Health and Wellness Encyclopedia (MacMillan Publishing Company,

1998) was honored as reference book of the year by the New York Public

Library, and the same honor was given in a previous year to Charles

Inlander et al., The People's Medical Society Health Desk Reference

(Hyperion Books, 1996).

* People’s Medical Society: About the Society, available at

<http:peoplesmed.org/abutmenu. html>.

. Q: How can I be checked for a B,, deficiency?

A: Blood tests are used. Usually a serum B,, test is done first.

If that’s low, physicians test to check for two other blood

components associated with B,, deficiency: homocysteine and

methylmalonic acid... .

Ellen Moyer, Vitamins & Minerals » Questions You Have. Answers You

Need 104 (People’s Medical Society, 1993).

\ “3

patent. In many instances, both sides in patent lawsuits have

incentives to argue in favor of patentability of broad types of

inventions and discoveries, even when challenging a

particular patent, because each side in the dispute has its own

patent portfolio it wants to protect or can readily pass royalty

charges on to the consumer.” In contrast, the People’s

Medical Society does not hold any patents and thus can raise

fundamental legal and policy concerns.

The lack of a mechanism for a consumer voice in the

process for granting a patent is particularly troublesome,

given the fact that much medical research in the United

States is funded by the public. Over $27,887,512,000 in

taxpayer funds were given to the National Institutes of Health

(NIH) for medical research in 2004.° In fact, according to the

‘658 patent, the inventors relied on government funding for

their work that led to the ‘658 patent. In addition, inventors’

medical articles note their use of federal funding. See, e.g.,

S.P. Stabler et al., Elevation of Total Homocysteine in the

Serum of Patients with Cobalamin or Folate Deficiency

Detected by Capillary Gas Chromatography -— Mass

Spectrometry, 81 J. Clin. Invest. 2, 466, 473 (February 1988).

The Court’s decision in this case will have a substantial

impact on patients, including those whose interests the

People’s Medical Society champions. It will also have an

impact on the services the non-profit People’s Medical

Society performs.

SUMMARY OF ARGUMENT

The U.S. Constitution, Article I, Section 8, Clause 8,

gives Congress the power “to promote the progress of

* Lori B. Andrews, Genes and Patent Policy. Rethinking Intellectual

Property Rights, 3 Nature Reviews Genetics 805-806 (October 2002).

* National Institutes of Health, About NIH, available at

<http://www.nih.gov/about/>, last updated on December 19, 2005.

-4.

Science and the useful Arts, by securing for limited Times to

Authors and Inventors the exclusive Right to their respective

Wnitings and Discoveries.” However, claim 13 of U.S.

Patent No. 4,940,658 patent is not a “discovery” as that word

is used in the Constitution, nor is it patentable subject matter

under 35 U.S.C. § 101. Rather, it is an unpatentable- law of

nature.

Unlike situations in which a law of nature is merely part

of a larger process, where the structure or process, when

considered as a whole, is performing a function which the

patent laws were designed to protect (e.g., transforming or

reducing an article to a different state or thing), claim 13 of

the “658 patent is nothing more than the naked patenting of a

“law of nature.” The Court’s unbroken line of precedents

preclude a finding of validity under 35 U.S.C. § 101 where a

law of nature regarding a vitamin deficiency is sought to be

patented in assays of any kind, whether inventive or not,

when coupled with “correlating” -- i.e., thinking about --

certain elevated results and vitamin deficiency. See, e.g.,

Diamond v. Diehr, 450 U.S. 175 (1981); Parker v. Flook,

437 U.S. 584 (1978); and Gottschalk v. Benson, 409 U.S. 63

(1972).

Upholding a patent centered on such “correlating” would

also obliterate the protection for First Amendment activities

provided by the Court’s bar on the patentability of abstract

ideas. The Federal Circuit’s holding that physicians are

culpable of direct infringement of claim 13 every time they

think about or diagnose the relationship between

homocysteine levels and a vitamin deficiency would have a

chilling effect on protected speech and _ thought.

Reaffirmation of this Court’s precedents on the patentability

of processes utilizing “laws of nature” is necessary to correct

the constitutional imbalance the Federal Circuit’s opinion

would strike between Article I, Section 8, Clause 8 and the

First Amendment of the U.S. Constitution.

Finally, upholding claim 13 of the ‘658 patent would

have untenable policy implications. Enforcement of claim 13

-5-

will have a negative impact on medical care, the

dissemination of medical information, and medical

innovation. Upholding claim 13 of the ‘658 patent would

also deter people from participating in medical research.

Consequently, it is appropriate to overturn the decision of the

Federal Circuit and hold invalid claim 13 of the ‘658 patent.

ARGUMENT

I. Background

The starting point for any analysis of patentability is the

question, “What did the patent applicant invent?” See, e.g.,

United States Patent and Trademark Office, Official Gazette

Notices, November 22, 2005, Section II. With respect to

claim 13 of U.S. Patent No. 4,940,658 (the ‘658 patent), what

did the patent applicant invent? Metabolite Laboratories, Inc.

and Competitive Technologies, Inc. (collectively

“respondents”) have not asserted that the patentee invented

all methods of assaying homocysteine; in fact, clearly it did

not since Abbott Laboratories invented another method, and

indeed, alternate means of measuring homocysteine were

available prior to the patent application and were disclosed in

the patent application. Rather, what the patentee claims to

have discovered is a relationship (correlation) between the

levels of homocysteine and a deficiency of cobalamin or

folate (vitamin deficiency). Under centuries of case law and

patent policy, this relationship is an unpatentable law of

nature.

The inventors in this case are physicians and scientists

from non-profit institutions -— Columbia-Presbyterian

Medical Center, Columbia University, and the University of

Colorado Health and Science Center. By analyzing blood

from patients and blood donors, they observed that patients

with a high level of homocysteine in their blood often had a

vitamin deficiency. The inventors created a test for

-6-

measuring homocysteine levels, which is the subject of

claims one through twelve of the ‘658 patent. Petitioner

Laboratory Corporation of America Holdings (LabCorp)

does not dispute that these claims are valid. It continues to

pay royalties when it uses that test.

However, the inventors went further and included claim

13:

A method for detecting a deficiency of cobalamin or

folate in warm-blooded animals comprising the steps >‘:

Assaying a body fluid for an elevated level of

total homocysteine; and

Correlating an _ elevated level of total

homocysteine in said body fluid with a deficiency of

cobalamin or folate.

As this Court noted in its request for comment from the

Solicitor General, claim 13 covers anyone who “measure[s]

the level of the relevant amino acids using any device,

whether the device is, or is not, patented; second, notice[s]

whether the amino acid level is elevated and, if so,

conclude[s] that a vitamin deficiency exists.” Laboratory

Corp. of Am. Holdings v. Metabolite Labs., Inc., 73 U.S.L.W.

3512, 3512 (U.S. Feb. 28, 2005). The Federal Circuit held

that LabCorp induced infringement of claim 13 of the ‘658

patent based solely on the publication to physicians of a law

of nature — the relationship between levels of homocysteine

and vitamin deficiency. Metabolite Labs., Inc. v. Lab. Corp.

of Am. Holdings, 370 F.3d 1354, 1365 (2004).

Astonishingly, the Federal Circuit also held that physicians

infringed claim 13 merely by thinking about the relationship

between homocysteine and vitamin deficiency. /d. at 1363-

1365.

x %

Il. Claim 13 of the ‘658 Patent Is Not Patentable Subject

Matter and Should be Held Invalid.

A. Claim 13 of the ‘658 Patent Is Not a “Discovery”

Within the Meaning of Article I, Section 8, Clause 8

of the U.S. Constitution.

The U.S. Constitution, Article I, Section 8, Clause 8,

grants Congress the power “to promote the progress of

Science and the useful Arts, by securing for limited Times to

Authors and Inventors the exclusive Right to their respective

Writings and Discoveries.”

Throughout the ‘658 patent, the patentee describes its

homocysteine assay (the patentability of which is not in

dispute) as an “invention” and the relationship between

homocysteine levels and vitamin deficiency as a

“discovery.”’ However, this discovery does not rise to the

level of a patentable discovery as contemplated by Article 1,

Section 8, Clause 8 of the Constitution.

The term “Discoveries,” as utilized in Article I, Section 8,

Clause 8, is synonymous with “inventions.” Writing in 1889,

a patent law scholar noted that someone “may invent a

machine, and may discover an island or law of nature. For

doing the first of these things, the patent laws may reward

him, because he is an inventor in doing-it; but those laws

cannot reward him for doing either of the others, because he

is not an inventor in doing either.” Albert A. Walker, Text-

Book of the Patent Laws of the United States of America 2-3

(L. K. Strouse & Co., 2d ed. 1889).

An “invention,” in the parlance of the

Constitution and early patent laws, is a new

creation consciously sought and successfully

” For example, in the “Summary of the Invention” section of the ‘658

patent, the relationship between homocysteine and vitamin deficiency is

said to have been “discovered.” U.S. Patent No. 4,940,658 col. 4, 1. 17.

-8-

reduced to practice by the inventor. A

“discovery,” as used in the same parlance, was

intended to denote a fortuitous creation of the

inventor and not merely something found by

him or her. Thus, an “invention” and a

“discovery” share the requirement that the

inventor create something original; the

difference between the two is that an

“invention” is consciously sought, while a

“discovery” is created unexpectedly. A

discovery in that era, as used in the

intellectual property law, denoted something

originating from the human intellect and not

merely learned by that intellect.

Linda J. Demaine and Aaron Xavier Fellmeth, Reinventing

the Double Helix: A Novel and WNonobvious

Reconceptualization of the Biotechnology Patent, 55 Stan. L.

Rev. 303, 370 (2002) (citation omitted).

The dichotomy between discoveries and inventions is

similarly recognized under the patent laws of other countries.

The European Patent Convention (EPC) requires an

“inventive step,” excluding mere “discoveries” from

patentable subject matter. See European Patent Convention,

Article 52(2) (1998). The EPC states that “discoveries,

scientific theories and mathematical methods” are not

regarded as patentable subject material. /d. The similarity

between Europe and the United States on this point is in

keeping with the thrust toward international intellectual

property harmonization.*

* “The Uruguay round of WTO negotiations introduced TRIPS into

GATT and bravely attempted to harmonize global patent systems with

uniform standards of protection... . Both the U.S. and the U.K. have

made changes to their laws in response to these provisions. .. .” Thomas

K. McBride, Jr., Patent Practice in London ~ Local Irternationalism:

How Patent Law Magnifies the Relationship of the United Kingdom with

-9-

Claim 13 of the ‘658 patent does not claim a discovery as

contemplated by the U.S. Constitution, Article I, Section 8,

Clause 8; therefore, claim 13 should be held invalid. The

relationship between homocysteine levels and vitamin

deficiency is a law of nature that exists independent of

human intervention, invention, or manipulation. This

relationship existed in mammals long before it was

uncovered, so this correlation is not a new or an inventive

innovation, but only the description of existing natural

phenomenon, a law of nature. While “anything under the sun

that is made by man” might be patentable, Diamond v. Diehr,

450 U.S. 175, 182 (1980) (citation omitted), the relationship

of homocysteine to vitamin deficiency was not made by man.

Moreover, recognition of claim 13 of the ‘658 patent.

would also be contrary to the policies underlying Article I.

The underlying goal of Article I, Section 8, Clause 8 was to

“promote the progress of Science and the useful Arts,” a goal

that is not met in the case of a patent that restricts others from

using a law of nature in their inventions.

B. Claim 13 of the ‘658 Patent Operates as an

Unpatentable “Law of Nature” Under 35 U.S.C. §

101.

35 U.S.C. § 101 limits the categories of inventions that

are patentable, stating “(w)hoever invents or discovers any

new and useful process, machine, manufacture, or

composition of matter, or any new and useful improvement

thereof, may obtain a patent therefore, subject to the

conditions and requirements of this title.” This Court has

consistently held that laws of nature are not patentable.

“This Court has undoubtedly recognized limits to § 101 and

every discovery is not embraced within the statutory terms.

Europe, the United States and the Rest of the World, 2 Loy. U. Chi. Int’!

L. Rev. 31, 47 (2004-2005).

-10-

Excluded from such patent protection are laws of nature,

natural phenomena, and abstract ideas.” Diehr, 450 U.S. at

185. See also Diamond v. Chakrabarty, 447 U.S. 303, 309

(1980); Parker v. Flook, 437 U.S. 584 (1978), Gottschalk v.

Benson, 409 U.S. 63, 67 (1972); Funk Bros. Seed Co. v. Kalo

Inoculant Co., 333 U.S. 127, 130 (1948); O'Reilly v. Morse,

56 U.S. (15 How.) 62, 116 (1853); Le Roy v. Tatham, 55 U.S.

(14 How.) 156, 175 (1852).

This Court has pointed out that a scientific principle

“reveals a relationship that has always existed.” Flook, 437

U.S. at 593.” Consequently, “[p]henomena of nature, though

just discovered, mental processes, and abstract intellectual

concepts are not patentable, as they are the basic tools of

scientific and technological work.” Benson, 409 U.S. at 71-

72. In Funk Bros., 333 U.S. at 130-131, the Court

recognized that unpatentable laws of nature include

biological phenomenon affecting naturally-occurnng living

organisms and held invalid a patent on a mixed culture of

bacteria for use in the inoculation of seeds. While noting that

the discovery was “ingenious,” the Court held, “He who

discovers a hitherto unknown phenomenon of nature has no

claim to a monopoly of it which the law recognizes.” /d. at

130.

* This logic is also underscored by the inherency doctrine in patent

law. For example, in a 2002 case, the Federal Circuit held that a patent

cannot t= granted to an applicant who has discovered a natura! attribute

of a liv.ag entity. /n re Cruciferous Sprout Litigation, 301 F.3d 1343

(Fed. Cir. 2002). Im that case the Federal Circuit stated, “[T]he

glucosinolate content and Phase 2 enzyme-inducing potential of sprouts

necessarily have existed as long as sprouts themselves, which is certainly

more than one year before the date of application... .” /n re Cruciferous

Sprout Litigation, 301 F.3d at 1350. Similarly, in the case at bar, the

inventors did not create the relanonship between homocysteine and

vitamun deficiency. That relationship, like the enzyme-inducing potential

of certain sprouts or the strength of pure tungsten (see General Electric

Co. v. DeForest Radio Co., 28 F.2d 641, 643 (3d Cir. 1928), cert. denied

278 U.S. 656 (1929)), previously existed in nature.

he

There are good policy reasons for not granting a patent

applicant a patent on a law of nature. The Court in Morse, 56

U.S. (15 How.) at 113, expressed its concern that granting

Samuel Morse broad rights to a law of nature for a generic

purpose (the use of electromagnetic waves to write at a

distance) beyond its particular application in Morse’s

concrete novel invention (the telegraph) would

- overcompensate the inventor by giving him rights to

subsequent inventions that he himself did not create that used

the law of nature governing electromagnetic waves. The

Court was also concerned that such a large grant of rights

would deter other inven’ors to the public’s detriment. /d at

120-121.

The Court denied Morse’s broad patent claim, stating:

If this claim can be maintained, it matters not

by what process or machinery the result is

accomplished. For aught that we now know

some future inventor, in the onward march of

science, may discover a mode of writing or

printing at a distance by means of the electric

or galvanic current, without using any part of

the process or combination set forth in the

plaintiff's specification. His invention may be

less complicated -- less liable to get out of

order -- less expensive in construction, and in

its Operation. But yet if it is covered by this

patent the inventor could not use it, nor the

public have the benefit of it without the

permission of this patentee.

Id. at 113.

The Court’s concern in Morse has come to pass in this

case. Abbott Laboratories invented an alternative test for

homocysteine levels that can be performed more efficiently,

but use of it to assess the likelihood of vitamin deficiency is

an infringement of the overly-broad patent claim 13 under

-12-

the logic of the Federal Circuit’s decision. This holding

gives patent rights not only to the test that the ‘658 patent

inventors themselves patented, but to any test invented by

anyone else that makes use of the law of nature about the

relationship between elevated homocysteine levels and

vitamin deficiency, even if that other test is more reliable,

less expensive, simpler i i use Or operation, or performed by a

new machine. °

C. Claim 13 of the ‘658 Patent Is Distinguishable From

an Allowable Patent Claim Which Merely

Incorporates a Law of Nature in a Larger, Patentable

Process.

Despite the patentee’s attempt to couch the claim as a

two-step process, claim 13 is a naked patent claim on a law

of nature and not a process within the meaning of 35 U.S.C.

§ 101. A process, as described by this Court in Cochrane v.

Deener, 94 U.S. 780 (1877), and reaffirmed in Diehr, is a

“mode of treatment of certain materials to produce a given

result. It is an act, or a series of acts, performed upon the

subject-matter to be transformed and reduced to a different

state or thing.” Diehr, 450 U.S. at 183 (quoting Cochrane,

94 U.S. at 788). The Court in Diehr stated further,

“transformation and reduction of an article ‘to a different

state or thing’ is the clue to the patentability of a process

claim that does not include particular machines.” /d. at 184

(quoting Benson, 409 U.S. at 70).

It is undisputed that there is no “particular machine” to be

utilized in claim 13. Nor can it be seriously maintained that

there is a “transformation and reduction of an article to a

_ "While Metabolite might argue that an alternative homocysteine test

could be used without infringing claim 13 if the physician using the test

does not then think about the relationship of the test results of vitamun

deficiency, Metabolite’s own witness, one of the inventors of the ‘658

patent, said physicians would necessarily think about that relationship or

risk a malpractice lawsuit. Metabolite Labs.. inc., 370 F.3d at 1364.

-13-

different state or thing” where any test, transforming or not,

can provide the data that is called for by the first step.

Even if it could be shown that transforming is a necessary

feature of all “assays,” even those yet to be invented, it is

clear that any such transformation is not the essence of the

purported process in claim 13 as it was in Diehr. There the

patentee transformed raw rubber into a final product usable

by consumers. Transformation was the point of the process.

Here, the acquisition of data, i.e., the number representing the

patient’s homocysteine level, is the sole purpose of the first

step. The mere gathering of data to apply a mathematical

formula should not make the formula patentable, in the same

way that imconsequential postsolution activities cannot

convert an unpatentable principle into a patentable process.

Flook, 437 U.S. at 590. Since the second step of claim 13 is

merely a mental step, a conclusion based upon the scientific

principle that elevated homocysteine levels mean vitamin

deficiency in a certain percentage of the cases,'' there is no

process here. Data is gathered, and in a physician’s mind a

scientific principle is applied and a conclusion is drawn.

That is all. '

In addition, the file wrapper history in this case should

estop Metabolite from claiming that claim 13 covers a two-

step process. The history of this case shows an attempt to

claim the use of a law of nature in a sweeping range of

technologies as was prohibited in the Morse case. The

patentee orginally resisted adding a discrete separate step for

claim 13 that would reveal enablement under 35 U.S.C. §

112, with the stunning party admission as follows:

'' According to a study of 7,747 patients in the ‘658 patent, the

percentage of patients with vitamun deficiency accurately predicted by the

test of homocysteine 1s 89%. Eleven percent of people with the vitamin

deficiency are mussed by the test. Moreover, 12% of healthy people on

whom the homocysteine test and correlation are used will erroneously be

told they have a vitamin deficiency. Because the test is not perfect, it is

important not to deter subsequent innovation.

-14-

“{A]s applicants are the first to detect cobalamin or

folate deficiency by assaying body fluids for total

homocysteine, it is believed that they are entitled to a

claim of equivalent scope, not limited to any particular

steps or methods.”

Metabolite, 370 F.3d at 1362 (emphasis added).

Since step | of claim 13 specifies any kind of assaying

for an elevated level of total homocysteine, and thus does not

involve an inventive aspect, the Federal Circuit focused on

step 2, “[t}he correlating step [which] is a simple conclusion

that a cobalamin/folate deficiency exists vel non based on the

assaying step. The patentee did not conceal or fail to disclose

this correlation, but instead featured it as the centerpiece of

the invention.” Jd. at 1367. Moreover, “the record shows

repeatedly that the correlating step is well within the

knowledge of one of skill in this art.” Jd. In short, there is

no valid process patent when the applicant admits there is no

process to begin with.

Patent law does not allow for exclusive control over a law

of physiology, even if such a natural phenomenon is

observed in a blood draw. Adding a “correlating” step to a

process that is devoid of any other inventive step or aspect

does not change that result. Moreover, thinking about a

physiological principle is not a “process” or “method” or

“art” wnder patent law. Rather, it is core First Amendment

activity, unpatentable ideation.

However, assuming arguendo that the Court finds that

claim 13 constitutes a “process,” that process is more

analogous to the processes found not to be patentable in

Benson and Flook than to the Diehr process.

Benson and Flook hold that the process itself must be

new and useful because the law of nature (or, in those cases,

the mathematical algorithm) “whether known or unknown at

the time of the claimed invention, [is]... one of the “basic

tools of scientific and technological work,’ see Gottschalk v.

-15-

Benson, 409 U.S. at 67, and is treated as though it were a

familiar part of the prior art.” Flook, 437 U.S. at 591-92.

Under the standards of Benson and Flook, neither of the

steps of claim 13 present an inventive aspect. Step one, the

assay, fails because there is not a specific new and useful

process involved. Rather, the patentee claims all assays for

homocysteine, no matter what kind and no matter who

actually inventea the assay, without any means of

enablement for the assays claimed. The second step, the

application of the correlation, fails because it is merely the

naked application of a law of nature, which is a basic tool of

scientific work.

This contrasts greatly with the patentable process using a

mathematical formula in Diehr. That was a specific process

involving multiple steps,’? involving a particular machine,

"? There were three claims at issue in Diehr, 450 U.S. at 179. The

first claimed:

1. A method of operating a rubbe- :nolding press for precision

molded compounds with the aid of a digital computer, comprising:

‘providing said computer with a data base for said press

including at least,

‘natural Jogarithm conversion data (1n),

‘the activation energy constant (C) unique to each batch of

said compound being molded, and

‘a constant (x) dependent upon the geometry of the

particular mold of the press,

‘mmitiating an interval timer in said computer upon the

closure of the press for monstoring the elapsed time of said

closure,

‘constantly determining the temperature (Z) of the mold at a

location closely adjacent to the mold cavity in the press during

molding,

‘constantly providing the computer with the temperature

(Z),

‘repetitively calculating in the computer, at frequent

intervals during each cure, the Arrhenius equation for reaction

tume during the cure, which 1s

‘In v <vl>equ CZ+x

‘where v is the total required cure time,

-16-

used for a specific application. In Diehr, this Court

distinguished between process claims containing scientific

principles “where the structure or process, when considered

as a whole, is performing a function which the patent laws

were designed to protect (e.g., transforming or reducing an

article to a different state or thing)”, 450 U.S. at 192, and

those which are “seeking patent protection for [a] formula in

the abstract,” aided by a competent draftsman. /d. at 191.

Claim 13 of the ‘658 patent does not seek patent

protection for the patentee’s assay for homocysteine levels.

That protection is claimed by other claims in the patent and is

not here in dispute. What then does claim 13 add to the other

claims? The answer is obviously the protection of the

discovery of the relationship between elevated homocysteine

levels and vitamin deficiency. Is this discovery the type that

the patent laws were designed to protect? No, since it is most

clearly a law of nature. By adding a step of using any means

of gathering data, whether patentable or not, to apply in a law

of nature, does the process as a whole become something the

patent laws were designed to protect or is it still just the law

of nature, claimed through a clear subterfuge of a competent

draftsman? All laws of nature require the input of data to

apply the law. Hence, any such law could be drafted as a two

or three step process, e.g. obtain a reading for x, apply the

law that x = y, conclude y.

This purported process contains none of the touchstones

this Court has used to winnow properly protectable process

claims from the overreaching claims of those who discovered

natural laws and sought to monopolize them. It does,

however, contain a cleverly drafted breakdown of a one-step

scientific principle into a purported two-step process. It is

‘repetitively comparing in the computer at said frequent

intervals during the cure each said calculation of the total

required cure time calculated with the Arrhenius equation and

said elapsed time, and

‘opening the press automatically when a said comparison

indicates equivalence.’

At

precisely the type of claim this Court sought to prevent in

Benson and Flook.

Moreover, the Federal Circuit ruled that claim 13 of the

‘658 patent is infringed simply by a physician thinking in his

or her head after receiving the results of a body fluid assay

that the level of homocysteine is or is not correlated to a

vitamin deficiency of cobalamin or folate. Metabolite Labs.,

Inc., 370 F.3d at 1363-1365. This thought process proceeds

entirely inside the physician’s head and is essentially, a

physician applying a biological fact to his patient. The

physician’s mere thoughts were found to be infringement.

Yet, mental processes have specifically been ruled by the

Supreme Court to be unpatentable subject matter in Benson,

409 U.S. at 67, and Flook, 437 U.S. at 589, so this step alone

cannot serve as a basis to uphold claim 13.

The potential harms to the public in upholding an

inappropriate claim on a law of nature involving a medical

fact are particulaily grave. Erroneously granted patents on

computer programs or a business method are unlikely to kill

someone. Discouraging physicians from learning about or

thinking about a medical fact could.

Ill. Patent Protection for Claim 13 of the ‘658 Patent Chills

the Exercise of First Amendment Rights.

Both the patent law and the First Amendment have a

common goal: to encourage the expansion of knowledge

through disclosure. The patent law encourages disclosure of

inventions to seed future innovation in the technological

sphere. See, e.g. Bonito Boats, Inc. v. Thunder Craft Boats,

Inc., 489 U.S. 141, 151 (1989) (“the ultimate goal of the

patent system is to bring new designs and technologies into

the public domain through disclosure”). The First

Amendment encourages a marketplace of ideas. U.S. Const.,

amend. I.

When the U.S. Patent and Trademark Office grants a

patent that can be used to prohibit a physician from thinking

-18-

about a medical fact, and prohibits anyone other than the

patent holder from publishing that medical fact, First

Amendment values are implicated.

A. Claim 13 of the ‘658 Patent Chills the Exercise of

Freedom of Thought.

Certain mghts are inherent in the expressly enumerated

nights of speech and the press and must be preserved to

effectuate the principles of the First Amendment. For

example, this Court has consistently recognized the

importance of freedom of thought, the ability to form or hold

a belief prior to its expression, as a right inherent in the First

Amendment. See Wooley v. Maynard, 430 U.S. 705, 714-

715 (1977); Palko v. Connecticut, 302 U.S 319, 326-327

(1937). This is in keeping with precedents recognizing that

the First Amendment protects other activities which are

precursors necessary to the formulation of expression,

communication and publication. Richmond Newspapers v.

Virginia, 448 U.S. 555, 556 (1980); Globe Newspaper Co. v.

Superior Court, 457 U.S. 596, 604 (1982).

Freedom of thought is a fundamental right necessary for

the existence of freedom of speech and of the press. “The

guarantee of free expression...is inextricably linked to the

protection and preservation of open and unfettered mental

activity.” Laurence Tribe, American Constitutional Law §

15-7, at 1322 (2d ed. 1988). As Justice Cardozo stated,

“freedom of thought...is the matrix, the indispensable

condition, of nearly every other form of freedom. With rare

aberrations a pervasive recognition of that truth can be traced

in our history, political and legal.” Palko, 302 U.S. at 326-

327.

In this case, the Federal Circuit stated that “the parties

hinge the direct infringement issue solely on whether the

physicians perform the correlating step,” Metabolite Labs.,

Inc., 370 F.3d at 1364, even though that correlation was done

entirely in the physicians’ minds. Thus, the Federal Circuit

-19-

held that the physicians directly infringed Metabolite’s claim

13 by thinking that a homocysteine level may signify a

vitamin deficiency. | Consequently, the granting and

enforcement of claim 13 chills the exercise of freedom of

thought.

The progress of scientific achievement is imperiled when

a patent claim such as claim 13 asserts as private intellectual

property basic scientific information. Because of the

enforcement of claim 13, physicians in clinics and in research

institutions will be prohibited from thinking about the

correlation between elevated levels of homocysteine and

vitamin deficiency unless they pay the toll of using

Metabolite’s test.

B. Claim 13 of the ‘658 Patent Chills the Exercise of

Freedom of Speech.

The Federal Circuit held that LabCorp indirectly

infringed claim 13 of the ‘658 patent by publishing basic

scientific information. /d. at 1364-65. Such a holding chills

the exercise of freedom of speech. This result denies

physicians hoping to treat ill patients access to basic

scientific information and restricts the ability of other

scientists to undertake further research regarding the

information and publish the results of that research.

The slim reason why over $4 million in damages were

assessed against LabCorp was that they induced infringement

by publishing an article about the homocysteine-vitamin

deficiency relationship. But it is difficult to imagine how the

publication of a previously-known and previously-published

fact could be found to have induced infringement. Arguably,

LabCorp did not induce infringement when it informed

physicians about the relationship between homocysteine

levels and vitamin deficiency because physicians alread’,

knew about that relationship. In fact, the association is so

well-known that one of the inventors said it would violate the

standard of care for physicians not to apply that known

-20-

association.'? The '658 patent itself revealed the association.

At least 22 articles in the medical literature written by the

inventors themselves before the publication of the LabCorp

article disclosed the correlation.'* In addition, other

physicians and scientists published articles in the medical

literature revealing that correlation. '°

'? The inventor said “that it would be malpractice for a physician to

receive a total homocysteine assay without determining cobalamin/folate

deficiency.” Metabolite, 370 F.3d at 1364.

'* A search of www.pubmed.gov, which is a search engine provided

by the National Center for Biomedical Information, the National Library

of Medicine, and the National Institute of Health created to disseminate

biomedical information, located 22 articles that disclosed the

homocysteine and vitamin deficiency correlation prior to the date

Laboratory Corporation of America distributed its publication of the

correlation to physicians. See e.g., AM. Kuzmunski et al., Effective

Treatment of Cobalamin Deficiency with Oral Cobalamin, 92 Blood 4,

1191-98 (1998); A.E. Sumner et al., Elevated Methylmalonic Acid and

Total Homocysteine Levels Show High Prevalence of Vitamin B;:

Deficiency After Gastric Surgery, 124 Ann. Intern. Med. 5, 469-76

(1996); J. Lindenbaum et al., Prevalence of Cobalamin Deficiency in the

Framingham Elderly Population, 60 Am. J. Clin. Nutr. 1, 2-11 (1994);

D.G. Savage et al., Sensitivity of Serum Methylmalonic Acid and Total

Homocysteine Determinations for Diagnosing Cobalamin and Folate

Deficiencies, 96 Am. J. Med. 3, 239-46 (1994); S.P. Stabler et al.,

Elevation of Total Homocysteine in the Serum of Patients with

Cobalamin or Folate Deficiency Detected by Capillary Gas

Chromography-Mass Spectrometry, 81 J. Clin. Invest. 2, 466-74 (1988).

'S See e.g., H. Ono et al., Plasma Total Homocysteine Concentrations

in Epileptic Patients Taking Anticonvulsants, 46 Metabolism 8, 959-62

(1997); S.E. Miner et al., Clinical Chemistry and Molecular Biology of

Homocysteine Metabolism: An Update, 30 Clin. Biochem. 3, 189-20!

(1997); E. Joosten et al., /s Metabolic Evidence for Vitamin B-/2 and

Folate Deficiency More Frequent in Elderly Patients with Alzheimer's

Disease’, 52 J. Gerontol A. Biol. Sci. Med. Sci. 2, M76-9 (1997); J. Metz

et al., The Significance of Subnormal Serum Vitamin B,, Concentration in

Older People: A Case Control Study, 44 J. Am. Genatr. Soc. 11, 1355-61

(1996), Jensen M. Krogh et al., Folate and Homocysteine Status and

Haemolysis in Patients Treated with Sulphasalazine for Arthritis, 56 Scan

J. Clin. Lab. Invest. 5, 421-9 (1996); E. Joosten et al., Cobalamin

Absorption and Serum Homocysteine and Methylmalonic Acid in Elderly

#4.

By prohibiting further publication of the homocysteine-

vitamin deficiency relationship, enforcement of claim 13 runs

afoul of this Court’s First Amendment holdings that “the

state may not, consistently with the spint of the First

Amendment, contract the spectrum of available knowledge.”

Griswold v. Connecticut, 381 U.S. 479, 482 (1965).

IV. Allowing Claim 13 of the ‘658 Patent to Stand as Valid

Would Have Untenable Policy Implications.

A. Upholding Claim 13 of the ‘658 Patent Would Have a

Negative Impact on Health Care in the U.S.

The enforcement of claim 13 of the ‘658 patent creates a

patent infringement when a physician thinks about a law of

nature, a medical fact. There is no fair use exception, unlike

in copyright law. 17 U.S.C. § 107. There is only a very

narrow research exception, so narrow as to be declared by

commentators as “for all practical purposes a nullity.” Janice

M. Mueller, The Evanescent Experimental Use Exemption

from the United States Patent Infringement Liability:

Implications for University and Nonprofit Research and

Development, 56 Baylor L. Rev. 917, 962 (2004). See also

Katherine J. Strandburg, What Does the Public Get?

Experimental Use and the Patent Bargain, 2004 Wis. L. Rev.

81, 87 (2004); Madey v. Duke Univ., 307 F.3d 1351, 1362

(Fed. Cir. 2002). This contrasts with the broad experimental

use exceptions in other countnes. Gen'l Secretariat of the

Council of the Eur. Communities, Records of the

Luxembourg Conference on the Community Patent 1973, art.

31(b), at 302; see also William R. Cornish, Experimental Use

of Patented Inventions in European Community States, 29

Int'l Rev. Indus. Prop. & Copyright L. 735, 735-36 (1998),

Subjects with Low Serum Cobalamin, 51 Eur. J. Haematol. 1, 25-30

(1993).

2.

Scrutiny of claim 13 of the ‘658 patent is particularly

important because it can affect people’s health. Vitamin

deficiency is a major-public health problem. It “can cause

senous illnesses in humans, including vascular disease,

cognitive dysfunction, birth defects and cancer. If detected

early enough, however, vitamin supplements readily treat the

deficiency.” Metabolite Labs., Inc, 370 F.3d. at 1358.

- If claim 13 of the ‘658 patent is declared valid, patients’

medical care will suffer. Physicians (other than those who

have ordered a test from the patent holder) will be deterred

(on penalty of patent infringement) from recognizing in their

patients the association between the level of homocysteine

and vitamin deficiency. It will also impede health care if,

every time a health care provider or medical laboratory

technician is about to diagnose a patient, he or she has to

stop, mid-thought, -and undertake an extensive patent

search.'°

International conventions about intellectual property

rights, to which the United States is a signatory, provide that

patent mghts should give way to health concems in certain

instances. For example, the Agreement on Trade Related

Aspects of Intellectual Property Rights of the World Trade

Organization, promulgated in 1995, highlights how public

health can be given greater weight than the commercial

concerms of patentees. Agreement on Trade-Related Aspects

of Intellectual Property Rights, Dec. 15, 1993, 33 I.L.M. 81

(1994) (hereinafter TRIPS). Article 27 of TRIPS specifically

'° Since the medical fact might, as in the case under consideration,

have been patented prior to 1996, physicians will have to do patent

searches for all medical facts, even though ultimately -some physicians

might be protected by the limited safe harbor for physicians under 35

U.S.C. § 287(c). Even with respect to post-1996 patents, however, the

protection of § 287 will not apply to other individuals who supply

medical information, such as a Ph.D. in genetics who applies a medical

correlation about a particular gene mutation and breast cancer, or a group

that publishes medical information, such as the People’s Medical Society.

-23-

allows governments to exclude from patentability diagnostic,

therapeutic, or surgical methods. /d.

The enforcement of claim 13 of the ‘658 patent increases

the cost of health care and impedes appropriate medical care

by improperly interfering with physicians’ and patients’

ability to gain information about a medical fact and to think

about that fact.

B. Upholding Claim 13 of the ‘658 Patent Would Have a

Negative Impact on the Dissemination of Medically

Relevant Information.

The enforcement of claim 13 of the ‘658 patent interferes

with the free flow of information about a scientific fact of

great relevance to the health of individuals. In this case, the

offending publication provides just the sort of information

that health care providers and consumers need — information

about both the diagnosis and treatment of vitamin deficiency.

Metabolite, 370 F.3d at 1365. If claim 13 is upheld, entities

that wish to publish information about the relationship

between homocysteine and a vitamin deficiency — a true

medical! fact — will be deterred from doing so by the cost of

paten. royalties or the possibility of millions of dollars in

damages for induced infringement.

The absurdity of Metabolite’s position in this case is

illustrated by the following example: it would not induce

infringement of claim 13 if the People’s Medical Society

published an article saying, “There are several tests for

homocysteine levels. We recommend that you get the test

from Abbott Laboratories.” However, if People’s Medical

Society attempted to further its non-profit mission by

providing information to consumers and added, “‘An elevated

level on a homocysteine test can indicate whether you have

vitamin deficiency,” that statement would induce

infringement of the patent. Clearly, claim 13 deters

publication of medical information.

-24-

Upholding claim 13 of the ‘658 patent would also create

an incentive for other companies to assert patent nghts over

other scientific facts, further increasing the cost of health care

and diminishing the flow of medical information.

C. Upholding Claim 13 Would Have a Negative Impact on

/nnovation.

Patent law has one underlying policy aim -- to encourage

innovation. The mechanism by which that is achieved is by

granting the patent holder a monopoly on any use of the

patented invention in exchange for a disclosure in the patent

application of how exactly the invention can be made. This

encourages innovation by stimulating people to invent in the

first place, often by making a better, cheaper, more

interesting, and more effective alternative to an existing

invention. Thus, if a person patents a mousetrap made of

wood, when the patent application later becomes public (a

condition of the patent grant), other inventors can read about

how the inventor made the mousetrap and can create novel

variations using significantly different materials or processes.

See Graham v. John Deere Co., 383 U.S. 1, 8-9 (1966).

Here, claim 13 deters innovation by preventing

researchers from thinking about or further exploring the

relationship of homocysteine and vitamin deficiency. Even

though another inventor could create a better homocysteine

test, perhaps one with a 99% correlation rather than the 89%

correlation of the Metabolite test, that inventor would not be

able to make his better test available because users of the test

would invanably think that the homocysteine levels

measured by the test were related to vitamin deficiency.

By chilling the publication of information about the

relationship between homocysteine levels and vitamin

deficiency, claim 13 will operate to deter researchers from

developing treatments for vitamin deficiency. In fact, if a

potential funder of research into treatments for vitamin

deficiency described the homocysteine-vitamin deficiency

-25-

relationship in a published solicitation for research proposals,

it could be liable for inducing infringement.

D. Upholding Claim 13 Would Deter People From

Participating in Medical Research.

Many patients served as research subjects and gave

generously of themselves so that the inventors of the ‘658

patent could recognize an inherent biological phenomenon,

the law of nature that high homocysteine levels correlate with

vitamin deficiency. According to the ‘658 patent, at least

301 of these patients were subjected to full clinical

evaluations including nsky neurological evaluations, blood

and bone marrow smears, and repeated serum tests for

antibodies to intrinsic factor for a period of two years. In all,

7,987 patients were studied and tested to discover the

patented relationship between homocysteine and vitamin

deficiency. There is no evidence in the patent or in the

publications by the inventors that the patients were informed

that medical information from their bodies would be

patented."

Upholding claim 13 is likely to have a deterrent effect on

people’s willingness to participate in research. Why should

someone altruistically give of their time and subject

themselves to potential physical risks if this leads to a patent

on a medical fact, increasing health care costs and deterring

innovation? As a result of this case, patients who are

potential research subjects are aware now that their altruistic

'’ Case law and medical ethics underscore the importance of such

disclosures. See, e.g. Moore v. Regents of the University of California,

51 Cal.3d 120, 793 P.2d 479 (1990). The AMA Code of Ethics Section

2.08 (3), provides “Human tissue and its products may not be used for

commercial purposes without the informed consent of the patient who

provided the original cellular material.” American Medical Association,

Council on Ethical! and Judicial Affairs, Code of Medical Ethics: Current

Opinions with Annotations, Section 2.08 Commercial Use of Human

Tissue (Chicago: AMA, 2000).

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participation in research, « ften at the cost of physical pain

and risk, might lead to medical facts being patented which

would increase the cost of their health care and interfere with

its quality. This is exactly what happened to the 7,987

people who participated in this study, some of whom had

painful bone marrow fluid extractions without knowing that

the law of nature discovered in their bodies would be

patented. It would be reasonable for people to lose interest in

being research subjects if the laws of nature discovered in

their bodies lead to patents that can be enforced to their

detriment.

E. Adherence to the Law of Nature Doctrine Will Not

Stifle Innovation.

The Court should not forsake its strict adherence to its

laws of nature non-patentability doctrine which is of

constitutional as well as statutory dimension. Both Article I,

Section 8, Clause 8 and the First Amendment provide

breathing room for the public domain of abstract ideas and

speech related to such a marketplace of ideas. Some amici

curiae might argue that adhering to the laws of nature

doctrine will stifle innovation, but that is unlikely. With the

laws of nature doctrine in place, this has been the most

innovative era in the nation’s history. Moreover, similar

fears of discouragement of innovation voiced to the Court by

the computer software industry during the Benson litigation

were wisely directed to Congress, and have since proven to

be misplaced. To the extent that the biotechnology sector

now wants to exempt itself from longstanding legal precedent

and to codify the Federal Circuit’s holding in this case, that

sector should also go first to Congress, to the extent such an

approach is not constitutionally futile. Whether applied to

new or old technology, the Court’s non-patentability of laws

of nature doctrine should be applied to all sectors with the

same “general strictness.” Cf Graham, 383 U.S. at 19

(1966); Chakrabarty, 447 U.S. at 309, 315-316.

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CONCLUSION

Metabolite’s success in transmuting the Patent Act into

an exclusive governmentally-issued license to preclude

physicians, health care publishers, bioscience researchers,

and citizens alike from merely thinking about a principle of

human physiology underscores the importance of the issue

presented. Upholding claim 13 of the ‘658 patent would be

in conflict with patent jurisprudence and First Amendment

values and is likely to retard, not promote, “the progress of

Science and the useful Arts.” The Court should reaffirm its

rule that one cannot patent “laws of nature, natural

phenomena, and abstract ideas,” Diehr, 450 U.S. at 185, even

if the patent applicant attempts to lay claim to such a law of

nature by fractionating a single claim to make it appear that it

relies on two, three, or more steps, where the only alleged

innovation in the various steps and process is a law of nature.

We urge the Court to reverse the Federal Circuit decision i

this case.

Respectfully submitted,

Lor! B. ANDREWS

Counsel of Record

DEBRA GREENFIELD

CLEMENTS RIPLEY

CHICAGO-KENT COLLEGE OF LAW

565 West Adams Street

Chicago, IL 60611

Tel: 312-906-5359

FRANCIS C. J. PIZZULLI

718 Wilshire Boulevard

Santa Monica, CA 90401

Tel: 310-451-8020

Counsel for Amicus Curiae

December 22, 2005