Watson Amicus Brief FC Myriad Hearing of July 20, 2012

UNITED STATES COURT OF APPEALS FOR THE FEDERAL CIRCUIT

2010-1406

THE ASSOCIATION FOR MOLECULAR PATHOLOGY, THE AMERICAN COLLEGE OF

MEDICAL GENETICS, THE AMERICAN SOCIETY FOR CLINICAL PATHOLOGY, THE

COLLEGE OF AMERICAN PATHOLOGISTS, HAIG KAZAZIAN, MD, ARUPA

GANGULY, Ph.D, WENDY CHUNG, MD, Ph.D, HARRY OSTRER, MD, DAVID

LEDBETTER, Ph.D, STEPHEN WARREN, Ph.D, ELLEN MATLOFF, M.S., ELSA REICH,

M.S., BREAST CANCER ACTION, BOSTON WOMEN�S HEALTH BOOK COLLECTIVE,

LISBETH CERIANI, RUNI LIMARY, GENAE GIRARD, PATRICE FORTUNE, VICKY

THOMASON, and KATHLEEN RAKER,

Plaintiffs-Appellees,

v.

UNITED STATES PATENT AND TRADEMARK OFFICE,

Defendant,

and

MYRIAD GENETICS, INC.,

Defendant-Appellant,

and

LORRIS BETZ, ROGER BOYER, JACK BRITTAIN, ARNOLD B. COMBE, RAYMOND

GESTELAND, JAMES U. JENSEN, JOHN KENDALL MORRIS, THOMAS PARKS, DAVID

W. PERSHING, and MICHAEL K. YOUNG, in their official capacity as Directors of the

University of Utah Research Foundation,

Defendants-Appellants.

Appeal from the United States District Court for the Southern District of

New York, in case no. 09-CV-4515, Senior Judge Robert W. Sweet

BRIEF FOR AMICUS CURIAE JAMES D. WATSON

IN SUPPORT OF NEITHER PARTY

Matthew J. Dowd

James H. Wallace, Jr.

WILEY REIN LLP

1776 K Street NW

Washington, DC 20006

(202) 719-7000

Attorneys for Amicus Curiae James D. Watson

TABLE OF CONTENTS

Page

INTEREST OF AMICUS CURIAE JAMES D. WATSON .....................................1

ARGUMENT .............................................................................................................2

I.

BECAUSE HUMAN GENES ARE UNIQUE AND CONVEY

INFORMATION ABOUT THE ESSENCE OF BEING HUMAN,

THEY SHOULD NOT BE PATENTED ........................................................2

II.

THE HUMAN GENOME PROJECT WAS INTENDED TO

BENEFIT ALL, NOT JUST SELECT COMPANIES....................................8

III.

PATENTS ON HUMAN GENES ARE NOT NECESSARY, BUT IF

THEY ARE GRANTED, COMPULSORY LICENSES SHOULD BE

REQUIRED TO ENSURE FAIR ACCESS..................................................12

IV.

RULE 29(c)(5) STATEMENT......................................................................15

V.

CONCLUSION..............................................................................................15

CERTIFICATE OF SERVICE

TABLE OF AUTHORITIES

Page

Buck v. Bell,

274 U.S. 200 (1927)..............................................................................................6

OTHER SOURCES

Alok Jha, Human Genome Project Leader Warns Against Attempts to Patent

Genes, The Guardian, June 24, 2010 .................................................................13

James D. Watson, The Double Helix (1968).............................................................1

Tom Walsh, et al., Detection of Inherited Mutations for Breast and Ovarian

Cancer Using Genomic Capture and Massively Parallel Sequencing, 107

Proceedings of the National Academy of Science USA 12,629 (2010).............13

James D. Watson, The Nobelist vs. The Film Star: DNA Restrictions

Attacked, Washington Post, May 14, 1978, at D1................................................8

James D. Watson, DNA: The Secret of Life (2003)..........................................11, 15

J.D. Watson & F.H.C. Crick,

A Structure for Dexoyribose Nucleic Acid, 171 Nature 737 (1953).....................3

James D. Watson & John Tooze,

The DNA Story: A Documentary History of Gene Cloning (1981) ....................7

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INTEREST OF AMICUS CURIAE JAMES D. WATSON

James D. Watson is the co-discoverer of the double helix structure of

deoxyribonucleic acid (�DNA�). For this discovery, he and his colleague, the late

Francis Crick (along with the late Maurice Wilkins for related work), were

awarded the Nobel Prize in Physiology or Medicine in 1962. See James D.

Watson, The Double Helix (1968).

Throughout his career, Dr. Watson has been at the forefront of recombinant

DNA research and advances in genetic engineering. From 1956 until 1976, Dr.

Watson was on the faculty of Harvard University, leading the effort to focus the

biology department on the then-emerging field of molecular biology. Starting in

1968, Dr. Watson was the director of Cold Spring Harbor Laboratory (�CSHL�).

From 1994 to 2004, he served as the president of CSHL, and from 2004 until 2007,

he was CSHL�s chancellor. Dr. Watson is now Chancellor Emeritus of CSHL.

Of particular pertinence to the present appeal is Dr. Watson�s role in the

Human Genome Project. In 1988, Dr. Watson was appointed Associate Director

for Human Genome Research of the National Institutes of Health (�NIH�) and, in

1989, Director of the National Center for Human Genome Research at the NIH. In

these positions, Dr. Watson lead the public effort to sequence the human genome.

Given the significance of the issue at hand, Dr. Watson wishes to write

directly to the Court.

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ARGUMENT

I. BECAUSE HUMAN GENES ARE UNIQUE AND CONVEY

INFORMATION ABOUT THE ESSENCE OF BEING HUMAN,

THEY SHOULD NOT BE PATENTED

I have read through the various opinions issued in this case.1 Although the

opinions admirably describe the scientific details of DNA and human genes, what

the Court misses, I fear, is the fundamentally unique nature of the human gene.

Simply put, no other molecule can store the information necessary to create and

propagate life the way DNA does. It is a chemical entity, but DNA�s importance

flows from its ability to encode and transmit the instructions for creating humans.

Life�s instructions ought not be controlled by legal monopolies created at the whim

of Congress or the courts.

Even before DNA�s structure was revealed, many scientists recognized the

importance of a cell�s chromosomes (which are composed of DNA) to the

propagation of life. In 1944, Erwin Schrﾚdinger, a Nobel Prize-winning physicist,

wrote a small book titled What Is Life? In it, he reasoned that chromosomes were

the genetic information bearers. Schrﾚdinger thought that, because so much

information must be packed into every cell, the information must be compressed

into �hereditary code-script� embedded in the molecular fabric of the

1 I have also read the Supreme Court�s decision in Mayo v. Prometheus, although

its opaqueness must leave many attorneys wondering if it adds anything at all to

the issue of whether human genes ought to be patented.

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chromosomes. At the time, this was an untested hypothesis; most biologists

thought that proteins would be identified as the bearers of genetic instruction.

Eventually, chemical techniques advanced, and scientists confirmed that the

chromosomes contained our genes.

As it turned out, the secret to DNA�s ability to create life is its double helical

structure, along with its information-coding sequences. Francis Crick and I

published the first correct structure of DNA in 1953. J.D. Watson & F.H.C. Crick,

A Structure for Dexoyribose Nucleic Acid, 171 Nature 737 (1953).2 The double-

helical structure epitomized elegance in simplicity. From a chemical perspective,

DNA is little more than two strands of a nucleotide polymer wound together in a

double helix formation. The nucleotide polymer consists of various sequences of

A, T, G, and C bases. The helical structure has two strands, one complementary to

the other.

As soon as Francis and I deciphered the structure, we immediately

understood its significance. With a hint of more to come, we wrote in our article

that �[i]t has not escaped our notice that the specific pairing we have postulated

immediately suggests a possible copying mechanism for the genetic material.�

The double helix structure confirmed DNA�s role as the genetic carrier and created

2 At the time, we were in a tight race with Linus Pauling (soon to be a Nobel

laureate in chemistry). Fortunately for us, Pauling concluded that DNA was a

triple helix�an erroneous conclusion ironically based on a chemical error.

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the possibility of almost limitless information storage. The various sequences of

bases could be translated by a cell�s machinery, and that information would be

used to create new proteins for the cell.3

Later scientists discovered that certain DNA sequences controlled the

expression of other genes. One of the earliest discovered of these control

sequences was the �TATA box.� The TATA box contains the core DNA sequence

5�-TATAAA-3� or a similar variant. Specific proteins can bind to this sequence,

which promotes the transcription of other specific genes. Extracted from the

chromosome, a nucleic acid molecule having the TATAAA sequence has little,

physically inherent value. Its significance arises because that sequence is useful

information to the cell�s genetic machinery. The TATAAA sequence leads to the

expression of genes that affect the cell and ultimately our human experience.

The terminology of DNA underscores DNA�s informational role in life. In a

living cell, DNA is used to make RNA, and then RNA is used to make

polypeptides, i.e., protein. The first step�DNA to RNA�is called transcription.

The second step�RNA to proteins�is called translation. Both words connote the

conveyance of information. The information encoded by a human gene is first

3 Amusingly, after I gave my first presentation of our DNA structure in June 1953,

Leﾗ Szilﾇrd, the Hungarian physicist and inventor of the nuclear chain reaction,

asked whether I would patent the structure. That, of course, was out of the

question.

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transcribed into RNA (DNA and RNA are similar molecules, thus similar

languages, so the genetic information is merely transcribed from one format to

another). Then, the genetic information is translated from RNA into protein.

(RNA and protein are different biochemical �languages,� hence translation). The

entirety of the DNA machinery focuses on transferring and utilizing the genetic

information.

When cells replicate, they make copies of the genetic code for the progeny

cells. New strands of DNA are synthesized in a process analogous to the way

scriveners of years past would copy legal documents. Just as scriveners would

copy legal documents word by word, a cell copies the DNA molecule letter by

letter (A, G, T, or C). And just as scriveners proofread their work, the DNA

polymerase�the enzyme that replicates DNA�has a built-in proofreading

mechanism. But as with all proofreading, the system is not perfect, and errors

occur. �Typographical� errors with DNA replication can lead to genetic

mutations�which can cause devastating diseases or can lead to evolutionary

improvements.

To this day, we continue to learn how human genes function. We estimate

that humans have approximately 22,000 genes. We have yet to fully understand

the functions of all human genes, but this lack of understanding is further reason

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that scientists should be permitted to experiment on human genes free from any

threat of patent infringement.

The social history of human genes also reveals DNA�s informational

uniqueness. In the early part of the twentieth century, many in society believed

that the answers to all of society�s ills resided in the human genome. From that

belief grew the eugenics movement�an ill-fated movement founded on an

incomplete understanding of genetics.

Even the legendary Supreme Court justice Oliver Wendell Holmes

misunderstood the role of genes in human development. In the landmark case of

Buck v. Bell, 274 U.S. 200, 207 (1927), Justice Holmes expressed a view about

genetics that prevailed during his time:

It is better for all the world, if instead of waiting to execute degenerate

offspring for crime, or to let them starve for their imbecility, society

can prevent those who are manifestly unfit from continuing their

kind. . . . Three generations of imbeciles are enough.

We now know that many factors affect a person�s mental acuity, genes being some

of them. But Justice Holmes and other supporters of the eugenics movement could

not appreciate, at that time, the precise role of the human gene.

In years to come, with the right advances in genetic engineering, we may

well be able to treat or rectify mental disabilities and physical diseases which today

are deemed incurable. Such hope is all the more reason that scientific research on

human genes should not be impeded by the existence of unnecessary patents.

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More importantly, we would not want one individual or company to monopolize

the legal right to the beneficial information of a human gene�information that

should be used for the betterment of the human race as a whole.

By the 1970s, the public�s perception of DNA had reached its nadir. Far

from being viewed as the vindicator of the wrongfully accused�as the public sees

it today�recombinant DNA technology was considered by many to be inherently

dangerous. Indeed, various interest groups wanted to ban recombinant DNA

research.4 Ironically, this hysteria seemed to begin after I participated in the first

scientific discussions exploring whether proposed regulations on DNA research

were necessary (at the Gordon Research Conference of Nucleic Acids in June

1973). Unfortunately, the initial ruminations mutated into full-fledged proposed

restrictions, issued from the Asilomar Conference in February 1974. Later, as the

hysteria increased, the National Institutes of Health (�NIH�) enacted regulations

governing recombinant DNA technology. The public discourse reached such a

fevered pitch that, in the summer of 1976, the Cambridge City Council declared a

three-month moratorium on recombinant DNA research in the city of Cambridge�

and therefore at Harvard University and the Massachusetts Institute of Technology.

4 I describe much of this history in one of my books. See James D. Watson & John

Tooze, The DNA Story: A Documentary History of Gene Cloning (1981).

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I, of course, did not favor these restrictions. At one point, I had to defend

recombinant DNA research from the attacks of the actor Robert Redford, who,

along with the Environmental Defense Fund, raised money to stop experiments

with recombinant DNA. See James D. Watson, The Nobelist vs. The Film Star:

DNA Restrictions Attacked, Washington Post, May 14, 1978, at D1. Eventually,

reason and objectivity prevailed, and scientists were free to conduct their

recombinant DNA research without absurd regulations.

My point with this overly brief and incomplete history of recombinant DNA

research is to illustrate how the major controversies associated with human genes

have arisen because human genes are much more than chemical compounds. The

myopic viewpoint thinks of a human gene as merely another chemical compound,

composed of various bases and sugars. But history and science teach us otherwise.

A human gene, which is a product of nature, is useful because it conveys vital

information. The human genome�s ability to be our instruction book on life

distinguishes it from other chemicals covered by the patent laws. No other

molecule carries the information to instruct a human zygote to become a boy or a

girl, a blonde or brunette, an Asian, African, or Caucasian.

II.

THE HUMAN GENOME PROJECT WAS INTENDED TO BENEFIT

ALL, NOT JUST SELECT COMPANIES

In addition to understanding the uniqueness of human DNA, I hope that an

awareness of the Human Genome Project�s history will guide the Court to the

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correct decision that human genes, as products of nature, should not be patented.

The Human Genome Project was started not to increase the profits of select

companies but to expand the our understanding of the human genome and make

this information available to all scientists.

The genesis of the Human Genome Project dates to the mid-1980s, when the

dual technological advances of recombinant DNA and computers opened the door

to deciphering the human genome. In June 1986, I organized a special session at

Cold Spring Harbor Laboratory to discuss the beginnings of what would become

the Human Genome Project. At that time, the U.S. Department of Energy had also

begun to focus on sequencing the genome. Other eminent scientists joined the

early effort, including Bruce Alberts, Sydney Brenner, and David Botstein.

Eventually, we published our report (from the National Academy of Sciences)

making the case for sequencing the human genome. With the support of James

Wyngaarden, then-head of NIH, and many others, the Human Genome Project

became reality.

In May 1988, I was appointed Associate Director for Human Genome

Research of NIH (and later, in 1989, became NIH�s Director of the National Center

for Human Genome Research). In these positions, my role was to oversee a

multimillion dollar budget and to organize what had become an international effort

to map the human genome. The United States was directing the project and carried

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out half of the work, while the rest was done mainly in the United Kingdom,

France, Germany, and Japan.

Even at the early stages of the project, we were concerned about the issue of

patenting human genes. Most, although not all, eminent scientists recognized that

human genes should not be monopolized by patents. I believed at the time�and

continue to believe�that the issue of patenting human genes went to the very crux

of whether the information encoded by human DNA should be freely available to

the scientific community. Some twenty years ago, I explained that patenting

human genes was lunacy, and I was not a lone voice.

Sadly, and to the detriment of scientific research, my view did not control

the policy decisions of NIH, which had filed for numerous patents covering human

genes. Even more egregious were the types of patents being filed on human genes.

Many of NIH�s patents described only small portions of a gene. For example, in

June 1991, an NIH official had urged Craig Venter, who at the time was working at

NIH, to file patent applications on several hundred new DNA sequences, even

though, in many instances, neither Venter nor NIH had any inkling of what those

sequences did. The following year, Venter listed over 2,000 more sequences in his

patent applications, still having no clue about the function of those sequences.

I expressed my objections to NIH management, but to no avail. To me, it

was clear that the goal of the Human Genome Project was to map and publish the

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human genome sequence for the scientific community. As the then-leader of the

project, I felt a particular obligation to do what I could. In my view,

[t]he Human Genome Project is much more than a vast roll call of As,

Ts, Gs, and Cs: it is as precious a body of knowledge as humankind

will ever acquire, with a potential to speak to our most basic

philosophical questions about human nature, for purposes of good and

mischief alike.

James D. Watson, DNA: The Secret of Life 172 (2003). In 1992, I publicly

opposed NIH�s decision to patent human genes. As a result, I was left with no

choice and was forced to resign from NIH that year. Patenting human genes was

not necessary to complete the Human Genome Project. Indeed, the international

effort was proceeding on schedule without any need to file patent applications on

human genes.

Less than fifteen years after its start, the Human Genome Project, along with

Celera Genomics, achieved success. On June 26, 2000, President Bill Clinton and

Prime Minister Tony Blair announced that the two groups had finished a working

draft, which was published for the public in February 2001. Gaps in the rough

draft were filled in by 2003�fifty years after Crick and I published the structure of

DNA. Scientists have used the data to estimate that humans have about 22,000

genes�in some sense a surprisingly small number compared to other organisms.

The Human Genome Project was a multi-agency, international effort. It was

funded in large part by taxpayer money, and the primary expectation was that the

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information derived from the sequenced human genes would be available for all

scientists to use. Unfortunately, a decade later, private companies are still trying to

unnecessarily restrict access to human genes and the information encoded in those

genes. This situation burdens all of society. Other scientists involved in the

Human Genome Project continue to warn about the harms caused by patenting

human genes. For instance, John Sulston, who received the 2002 Nobel Prize in

Physiology or Medicine, headed the British effort of the Human Genome Project.

He has explained that �many human genes have patent rights on them and this is

going to get in the way of treatment unless you have a lot of money.�5

III.

PATENTS ON HUMAN GENES ARE NOT NECESSARY, BUT IF

THEY ARE GRANTED, COMPULSORY LICENSES SHOULD BE

REQUIRED TO ENSURE FAIR ACCESS

As a third point, lawyers and judges misunderstand scientific research when

they contend that patent protection is necessary to encourage scientists to discover

human genes. A scientist does not�and should not�expect to obtain a legal

monopoly controlling the information encoded by human genes. And the average

scientist should not expect a windfall simply for revealing the sequence of DNA

bases that encode various genes. Research on human genes is one of those rare

endeavors which should be�and is done�with the understanding that, although

5 See Alok Jha, Human Genome Project Leader Warns Against Attempts to Patent

Genes, The Guardian, June 24, 2010, at http://www.guardian.co.uk/science/2010/

jun/24/human-genome-project-patent-genes.

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inventions based on those genes may later be commercialized, the genes

themselves are to be employed for the maximum benefits of humankind.

Consider also whether a biotechnology or pharmaceutical company derives

major revenue of human genes. From what I have seen, the answer is generally no.

Most biotechnology and pharmaceutical companies do not derive substantial

revenue from selling or licensing human genes. Rather, their primary revenue

source is much more likely their selling pharmaceuticals or actual research tools.

We should not be overly concerned that banning patents on human genes will

cause a detrimental loss of revenue.

Additionally, researchers are developing new medical diagnostic tools which

often rely on the use of multiple genes. For instance, investigators at the

University of Washington have developed parallel gene sequencing methods for

identifying of inherited mutations in breast and ovarian cancer genes. See Tom

Walsh, et al., Detection of Inherited Mutations for Breast and Ovarian Cancer

Using Genomic Capture and Massively Parallel Sequencing, 107 Proceedings of

the National Academy of Science USA 12,629 (2010). This group�s approach uses

multiple genes, not just the specific BRCA1 and BRCA2 genes in the Myriad

patents, to estimate cancer risk.

If each of the human genes used in a new multi-gene assay are subject to

patents, I fear that useful tests requiring multiple human genes will be

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unnecessarily delayed, become prohibitively expensive, or, worse yet, never be

made available to patients at all. For a new assay using hundreds of human genes,

the sea of patents and patent applications would create hundreds, if not thousands,

of individual obstacles to developing and commercializing the assay. The best

way, in my view, to resolve this problem is to eliminate the unnecessary patenting

of human genes.

If, for some reason, patents on human genes are deemed necessary, the next

best, albeit imperfect, solution is to require those patent holders to license the

patents to other researchers so that scientific progress is not obstructed. This is

often called a �compulsory license.� In my view, a compulsory license can

establish reasonable access to human genes and genetic information�which is

what scientists in general want, had the lawyers and courts not complicated

matters. Reasonable access facilitates scientific and social progress.

Compulsory licensing ensures that scientists and researchers will have

reasonable access to human genes and genetic information. Compulsory licensing

will attenuate the negative consequences of the genetic monopolies created by

patents. Implementing a compulsory license protocol will also reduce the risk that

a patient is denied access to life-saving medicines and technologies using human

genes and the information encoded in the genes.

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CERTIFICATE OF SERVICE

I hereby certify that on this day, June 15, 2012, two copies of the foregoing

BRIEF OF AMICUS CURIAE JAMES D. WATSON IN SUPPORT OF

NEITHER PARTY were served via first class mail on the following counsel for

the parties:

Gregory A. Castanias

Jones Day

51 Louisiana Avenue, N.W.

Washington, D.C. 20001

Counsel for Defendants-Appellants

Bruce Vignery

AARP Foundation Litigation

601 E Street, NW

Washington, DC 20049

Counsel for Amicus AARP

Barbara R. Rudolph

Finnegan, Henderson, Farabow,

Garrett & Dunner

901 New York Avenue, N.W.

Suite 1100

Washington, DC 20001-4413

Counsel for Amicus American

Intellectual Property Law

Association

Seth P. Waxman

Wilmer Hale

1875 Pennsylvania Avenue, N.W.

Washington, DC 20006

Counsel for Amici Biotech Industry

Organization et al.

Christopher A. Hansen

American Civil Liberties Union

125 Broad Street, 18th Floor

New York, New York 10004

Counsel for Plaintiffs-Appellees

Stephen B. Maebius

Foley and Lardner

3000 K Street, N.W., Suite 500

Washington, DC 20007

Counsel for Amicus Alnylam

Pharmaceuticals

Lori B. Andrews

Chicago-Kent College of Law

Illinois Institute of Technology

College of Law

565 West Adams Street

Chicago, IL 60661

Counsel for Amici American

Medical Association et al.

Erik P. Belt

McCarter & English

265 Franklin Street

Boston, MA 02110

Counsel for Amicus Boston Patent

Law Association

John L. Hendricks

Hitchcock Evert LLP

750 North St. Paul Street

Suite 1110

Dallas, Texas 75201

Counsel for Amici Canavan

Foundation et al.

Christopher M. Holman

5100 Rockhill Road

Kansas City, MO 64110

Counsel for Amici Christopher

Holman et al.

E. Richard Gold

Faculty of Law, McGill University

3664 Peel Street

Montreal, Quebec H3A 1W9

Counsel for Amici E. Richard Gold

et al.

Erika R. George

Loyola University Chicago School

of Law

25 E. Pearson

Chicago, IL 60611

Counsel for Amici Erika R. George and

Kali N. Murray

David S. Forman

Finnegan, Henderson, Farabow,

Garrett & Dunner

901 New York Avenue, N.W.

Washington, DC 20001-4413

Counsel for Amicus Genetic

Alliance

Larry Frierson

The Law Offices of Larry Frierson

3265 Lake County Highway

Calistoga, CA 94515

Counsel for Amici Cancer Council

Australia and Luigi Palombi

Jennifer Gordon

Baker Botts

30 Rockefeller Center

New York, NY 10112

Counsel for Amicus Croplife

International

Eileen M. Kane

Penn State Dickinson School of Law

328 Katz Building

University Park, PA 16802

Counsel for Amicus Professor

Eileen N. Kane

Maxim H. Waldbaum

Schiff Hardin

900 Third Avenue, 23rd Floor

New York, NY 10022

Counsel for Amicus Fﾎdﾎration

Internationale des Conseils en

Propriﾎtﾎ Industrielle (FICPI)

William G. Gaede, III

McDermott, Will & Emery

275 Middlefield Rd., Suite 100

Menlo Park, CA 94025

Counsel for Amici Genomic Health

et al.

J. Timothy Keane

Harness, Dickey & Pierce

7700 Bonhomme Avenue, Suite 400

St. Louis, MO 63105

Counsel for Amici Gilead Sciences

et al.

George Kimbrell

International Center for

Technology Assessment

660 Pennsylvania Ave., Suite 302

Washington, D.C. 20003

Counsel for Amici International

Center for Technology Assessment

et al.

Judy Deleon Jarecki-Black

Merial Limited

3239 Satellite Blvd.

Duluth, GA 30096

Counsel for Amicus Merial Limited

Debra L. Greenfield

UCLA Center for Society and

Genetics

Box 957221, 1323 Rolfe Hall

Los Angeles, CA 90095

Counsel for Amici National

Women�s Health Network et al.

Kurt G. Calia

Covington & Burling

1201 Pennsylvania Avenue, N.W.

Washington, DC 20004-2401

Counsel for Amicus Pharmaceutical

Research and Manufacturers of

America

Herbert C. Wamsley

Intellectual Property Owners

1501 M Street

Suite 1150

Washington, D.C. 20005

Counsel for Amicus Intellectual

Property Owners Association

Jacqueline Wright-Bonilla

Foley & Lardner LLP

3000 K Street, NW

Suite 500

Washington, D.C. 20007

Counsel for Amici Rosetta Genomics,

Inc. et al.

Kent D. McClure

Animal Health Institute

1325 G Street, NW, Suite 700

Washington, DC 20005

Counsel for Amicus Animal Health

Institute

Aaron Stiefel

Kaye Scholer

425 Park Avenue

New York, NY 10022

Counsel for Amicus Novartis Corp.

Mark R. Freeman

U.S. Department of Justice

950 Pennsylvania Avenue, N.W.

Room 7646

Washington, D.C. 20530

Counsel for Amicus Curiae United

States

Krista L. Cox Ann M. McCrackin

Universities Allied for Essential University of New Hampshire

Medicines 2 White Street

2625 Alcatraz Avenue Concord, NH 03301

No. 180 Counsel for Amicus University of New

Berkeley, CA 94705 Hampshire School of Law

Counsel for Amicus Universities Allied

for Essential Medicines

James J. Kelley Andrew Chin

Eli Lilly & Co. University of North Carolina School of

940 S. East Street Law

Dock 88 160 Ridge Road CB# 3380

Lilly Corp. Center � Drop Code 1104 Chapel Hill, NC 27599

Indianapolis, IN 46225 Counsel for Amici University of North

Counsel for Amicus Eli Lilly & Co. Carolina School of Law et al.

Francis Pizzulli

718 Wilshire Blvd.

Santa Monica, CA 90401

Counsel for Amicus The Southern

Baptist Convention

____________________

Matthew J. Dowd

Dated: June 15, 2012