Association for Molecular Pathology v. United States Patent & Trademark Office

United States Court of Appeals
for the Federal Circuit
__________________________
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, PHD, WENDY CHUNG, MD,
PHD, HARRY OSTRER, MD,
DAVID LEDBETTER, PHD, STEPHEN WARREN,
PHD, 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
ASSOCIATION FOR MOLECULAR v. PTO 2
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.
__________________________
2010-1406
__________________________
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.
____________________________
Decided: July 29, 2011
____________________________
CHRISTOPHER A. HANSEN, American Civil Liberties
Union Foundation, of New York, New York, argued for
plaintiffs-appellees. With him of the brief were SANDRA S.
PARK, ADEN FINE and LENORA M. LAPIDUS. Of counsel on
the brief were DANIEL B. RAVICHER and SABRINA Y.
HASSAN, Benjamin N. Cardozo School of Law, of New
York, New York.
GREGORY A. CASTANIAS, Jones Day, of Washington,
DC, argued for defendants-appellants. With him on the
brief were BRIAN M. POISSANT, LAURA A. CORUZZI and
EILEEN FALVEY, of New York, New York; and ISRAEL
SASHA MAYERGOYZ, of Chicago, Illinois. Of counsel were
3 ASSOCIATION FOR MOLECULAR v. PTO
BENJAMIN JACKSON and JAY Z. ZHANG, Myriad Genetics, of
Salt Lake City, Utah.
MARY M. CALKINS, Foley & Lardner LLP, of Washing-
ton, DC, for amicus curiae Alnylam Pharmaceuticals, Inc.
With her on the brief were STEPHEN B. MAEBIUS and
HAROLD C. WEGNER. Of counsel on the brief was DONNA
T. WARD, DT Ward, P.C., Groton, Massachusetts.
CHRISTOPHER M. HOLMAN, University of Missouri-
Kansas City School of Law, Kansas City, Missouri, for
amici curiae Christopher M. Holman and Robert Cook-
Deegan.
PAUL H. BERGHOFF, McDonnell Boehnen Hulbert &
Berghoff LLP, of Chicago, Illinois, for amicus curiae
Intellectual Property Owners Association. With him on
the brief were KEVIN E. NOONAN and JEFFREY P.
ARMSTRONG. Of counsel on the brief were DOUGLAS K.
NORMAN and KEVIN H. RHODES, Intellectual Property
Owners Association, of Washington, DC.
BARBARA R. RUDOLPH, Finnegan, Henderson,
Farabow, Garrett & Dunner, LLP, of Washington, DC, for
amicus curiae American Intellectual Property Law Asso-
ciation. With her on the brief were ROBERT D. LITOWITZ
and ERIKA HARMON ARNER; and ROBERT C. STANLEY, of
Atlanta, Georgia. Of counsel on the brief was DAVID W.
HILL, American Intellectual Property Law Association, of
Arlington, Virginia.
KENT D. MCCLURE, Animal Health Institute, of Wash-
ington, DC, for amicus curiae Animal Health Institute;
JUDY JARECKI-BLACK, Merial Limited, of Duluth, Georgia,
for amicus curiae Merial Limited.
ASSOCIATION FOR MOLECULAR v. PTO 4
SETH P. WAXMAN, Wilmer Cutler Pickering Hale and
Dorr LLP, of Washington, DC, for amici curiae Biotech-
nology Industry Organization and The Association of
University Technology Managers. With him on the brief
were THOMAS G. SAUNDERS; MARK C. FLEMING and ALLEN
C. NUNNALLY, of Boston, Massachusetts. Of counsel on
the brief was HANS SAUER, Biotechnology Industry Or-
ganization, of Washington, DC.
ERIK PAUL BELT, McCarter & English, LLP, of Boston,
Massachusetts, for amicus curiae Boston Patent Law
Association. With him of the brief were LEE CARL
BROMBERG and MARIA LACCOTRIPE ZACHARAKIS.
JENNIFER GORDON, Baker Botts, LLP, of New York,
New York, for amicus curiae CropLife International.
With her on the brief were STEVEN LENDARIS and
JENNIFER C. TEMPESTA.
MAXIM H. WALDBAUM, Schiff Hardin LLP, of New
York, New York, for amicus curiae Federation Interna-
tionale Des Conseils en Propriete Industrielle.
DAVID S. FORMAN, Finnegan, Henderson, Farabow,
Garrett & Dunner, LLP, of Washington, DC, for amicus
curiae Genetic Alliance. With him on the brief were
CHARLES T. COLLINS-CHASE, BRENDA J. HUNEYCUTT,
JENNIFER A. JOHNSON, and LAURA P. MASUROVSKY;
MUKTA JHALANI, of Palo Alto, California; and MARY R.
HENNINGER, of Atlanta, Georgia. Of counsel on the brief
was ANN WALDO, Genetic Alliance, Inc., of Washington,
DC.
WILLIAM G. GAEDE, III, McDermott Will & Emery
LLP, of Menlo Park, California, for amici curiae Genomic
5 ASSOCIATION FOR MOLECULAR v. PTO
Health, Inc., et al. With him on the brief was ANDREW A.
KUMAMOTO.
BRIAN R. DORN, Merchant & Gould, P.C., of Minneapo-
lis, Minnesota, for amicus curiae Kane Biotech Inc. With
him on the brief was KATHERINE M. KOWALCHYK.
AARON STIEFEL, Kaye Scholer LLP, of New York, New
York, for amicus curiae Novartis Corporation. Of counsel
on the brief was SYLVIA M. BECKER, of Washington, DC.
KURT G. CALIA, Covington & Burling, LLP, of Red-
wood Shores, California, for amicus curiae Pharmaceuti-
cal Research and Manufacturers of America. Of counsel
on the brief were ROBERT A. LONG, JR. and ALLISON E.
KERNDT, of Washington, DC.
JACQUELINE D. WRIGHT BONILLA, Foley & Lardner
LLP, of Washington, DC, for amici curiae Rosetta Genom-
ics, Ltd., et al. With her on the brief was RICHARD C.
PEET. Of counsel on the brief was GEORGE C. BEST, of
Palo Alto, California.
MARK R. FREEMAN, Attorney, Appellate Staff, Civil
Division, United States Department of Justice, of Wash-
ington, DC, for amicus curiae United States. With him on
the brief were TONY WEST, Assistant Attorney General,
BETH S. BRINKMANN, Deputy Assistant Attorney General,
and SCOTT R. MCINTOSH, Attorney.
ANN M. MCCRACKIN, University of New Hampshire
School of Law, of Concord, New Hampshire, for amicus
curiae University of New Hampshire School of Law. With
her on the brief was J. JEFFREY HAWLEY.
ASSOCIATION FOR MOLECULAR v. PTO 6
J. TIMOTHY KEANE, Harness, Dickey & Pierce, P.L.C.,
of St. Louis, Missouri, for amici curiae Gilead Sciences,
Inc., et al.
LARRY FRIERSON, The Law Offices of Larry Frierson,
of Calistoga, California, for amici curiae Cancer Council
Australia and Luigi Palombi.
LORI B. ANDREWS, Chicago-Kent College of Law, of
Chicago, Illinois, for amici curiae American Medical
Association, et al. With her on the brief was JOSHUA D.
SARNOFF, DePaul University College of Law, of Chicago,
Illinois.
EILEEN M. KANE, Penn State Dickinson School of Law,
of University Park, Pennsylvania, amicus curiae.
JAMES P. EVANS, University of North Carolina, of
Chapel Hill, North Carolina
for amici curiae E. Richard Gold, James P. Evan and
Tania Bubela. With him on the brief were E. RICHARD
GOLD, McGill University, of Montreal, Quebec, Canada;
and TANIA BUBELA, University of Alberta, of Edmonton,
Alberta, Canada,
ERIKA R. GEORGE, Loyola University-Chicago School
of Law, of Chicago, Illinois, for amici curiae Erika R.
George and Kali N. Murray.
ANDREW CHIN, University of North Carolina School of
Law, of Chapel Hill, North Carolina, for amicus curiae
Professor Andrew Chin.
FRANCIS PIZZULLI, of Santa Monica, California, for
amicus curiae The Southern Baptist Convention.
7 ASSOCIATION FOR MOLECULAR v. PTO
JOHN L. HENDRICKS, Hitchcock Evert LLP, of Dallas,
Texas, for amici curiae Canavan Foundation, et al. With
him on the brief were MEGAN M. O’LAUGHLIN and JOHN T.
TOWER.
GEORGE A. KIMBRELL, The International Center for
Technology Assessment, of Washington, DC, for amici
curiae The International Center for Technology Assess-
ment, et al.
KRISTA L. COX, Universities Allied for Essential Medi-
cines, of Berkeley, California, for amicus curiae Universi-
ties Allied for Essential Medicines.
BRUCE VIGNERY, AARP Foundation Litigation, of
Washington, DC, for amicus curiae AARP. With him on
the brief was MICHAEL SCHUSTER.
DEBRA L. GREENFIELD, UCLA Center for Society and
Genetics, of Los Angeles, California, for amici curiae The
National Women’s Health Network, et al.
__________________________
Before LOURIE, BRYSON, and MOORE, Circuit Judges.
Opinion for the court filed by Circuit Judge LOURIE.
Opinion concurring in part filed by Circuit Judge MOORE.
Opinion concurring in part and dissenting in part filed by
Circuit Judge BRYSON.
LOURIE, Circuit Judge.
Myriad Genetics, Inc. and the Directors of the Univer-
sity of Utah Research Foundation (collectively, “Myriad”)
appeal from the decision of the United States District
Court for the Southern District of New York holding that
an assortment of medical organizations, researchers,
ASSOCIATION FOR MOLECULAR v. PTO 8
genetic counselors, and patients (collectively, “Plaintiffs”)
have standing under the Declaratory Judgment Act to
challenge Myriad’s patents. Assoc. for Molecular Pathol-
ogy v. U.S. Patent & Trademark Office, 669 F. Supp. 2d
365 (S.D.N.Y. 2009) (“DJ Op.”). Myriad also appeals from
the district court’s decision granting summary judgment
that all of the challenged claims are drawn to non-
patentable subject matter under 35 U.S.C. § 101. Assoc.
for Molecular Pathology v. U.S. Patent & Trademark
Office, 702 F. Supp. 2d 181 (S.D.N.Y. 2010) (“SJ Op.”).
We affirm in part and reverse in part.
On the threshold issue of jurisdiction, we affirm the
district court’s decision to exercise declaratory judgment
jurisdiction because we conclude that at least one plain-
tiff, Dr. Harry Ostrer, has standing to challenge the
validity of Myriad’s patents. On the merits, we reverse
the district court’s decision that Myriad’s composition
claims to “isolated” DNA molecules cover patent-ineligible
products of nature under § 101 since the molecules as
claimed do not exist in nature. We also reverse the dis-
trict court’s decision that Myriad’s method claim to
screening potential cancer therapeutics via changes in cell
growth rates is directed to a patent-ineligible scientific
principle. We, however, affirm the court’s decision that
Myriad’s method claims directed to “comparing” or “ana-
lyzing” DNA sequences are patent ineligible; such claims
include no transformative steps and cover only patent-
ineligible abstract, mental steps.
BACKGROUND
Plaintiffs brought suit against Myriad, challenging
the patentability of certain composition and method
claims relating to human genetics. See DJ Op., at 369-76.
Specifically, Plaintiffs sought a declaration that fifteen
claims from seven patents assigned to Myriad are drawn
9 ASSOCIATION FOR MOLECULAR v. PTO
to patent-ineligible subject matter under 35 U.S.C. § 101:
claims 1, 2, 5, 6, 7, and 20 of U.S. Patent 5,747,282 (“the
’282 patent”); claims 1, 6, and 7 of U.S. Patent 5,837,492
(“the ’492 patent”); claim 1 of U.S. Patent 5,693,473 (“the
’473 patent”); claim 1 of U.S. Patent 5,709,999 (“the ’999
patent”); claim 1 of U.S. Patent 5,710,001 (“the ’001
patent”); claim 1 of U.S. Patent 5,753,441 (“the ’441
patent”); and claims 1 and 2 of U.S. Patent 6,033,857 (“the
’857 patent”).
The challenged composition claims cover two “iso-
lated” human genes, BRCA1 and BRCA2 (collectively,
“BRCA1/2” or “BRCA”), and certain alterations, or muta-
tions, in these genes associated with a predisposition to
breast and ovarian cancers. Representative composition
claims include claims 1, 2, and 5 of the ’282 patent:
1. An isolated DNA coding for a BRCA1 polypep-
tide, said polypeptide having the amino acid se-
quence set forth in SEQ ID NO:2.
2. The isolated DNA of claim 1, wherein said
DNA has the nucleotide sequence set forth in SEQ
ID NO:1.
5. An isolated DNA having at least 15 nucleotides
of the DNA of claim 1.
SEQ ID NO:2 depicts the amino acid sequence of the
BRCA1 protein, and SEQ ID NO: 1 depicts the nucleotide
sequence of the BRCA1 DNA coding region. ’282 patent
col.19 ll.48-50.
All but one of the challenged method claims cover
methods of “analyzing” or “comparing” a patient’s BRCA
sequence with the normal, or wild-type, sequence to
identify the presence of cancer-predisposing mutations.
Representative method claims include claim 1 of the ’999
and ’001 patents:
ASSOCIATION FOR MOLECULAR v. PTO 10
1. A method for detecting a germline alteration in
a BRCA1 gene, said alteration selected from the
group consisting of the alterations set forth in Ta-
bles 12A, 14, 18 or 19 in a human which comprises
analyzing a sequence of a BRCA1 gene or BRCA1
RNA from a human sample or analyzing a se-
quence of BRCA1 cDNA made from mRNA from
said human sample with the proviso that said
germline alteration is not a deletion of 4 nucleo-
tides corresponding to base numbers 4184-4187 of
SEQ ID NO:1.
’999 patent claim 1 (emphases added).
1. A method for screening a tumor sample from a
human subject for a somatic alteration in a
BRCA1 gene in said tumor which comprises []
comparing a first sequence selected from the
group consisting of a BRCA1 gene from said tu-
mor sample, BRCA1 RNA from said tumor sample
and BRCA1 cDNA made from mRNA from said
tumor sample with a second sequence selected
from the group consisting of BRCA1 gene from a
nontumor sample of said subject, BRCA1 RNA
from said nontumor sample and BRCA1 cDNA
made from mRNA from said nontumor sample,
wherein a difference in the sequence of the
BRCA1 gene, BRCA1 RNA or BRCA1 cDNA from
said tumor sample from the sequence of the
BRCA1 gene, BRCA1 RNA or BRCA1 cDNA from
said nontumor sample indicates a somatic altera-
tion in the BRCA1 gene in said tumor sample.
’001 patent claim 1 (emphasis added).
The final method claim challenged by Plaintiffs is di-
rected to a method of screening potential cancer therapeu-
11 ASSOCIATION FOR MOLECULAR v. PTO
tics. Specifically, claim 20 of the ’282 patent reads as
follows:
20. A method for screening potential cancer
therapeutics which comprises: growing a trans-
formed eukaryotic host cell containing an altered
BRCA1 gene causing cancer in the presence of a
compound suspected of being a cancer therapeu-
tic, growing said transformed eukaryotic host cell
in the absence of said compound, determining the
rate of growth of said host cell in the presence of
said compound and the rate of growth of said host
cell in the absence of said compound and compar-
ing the growth rate of said host cells, wherein a
slower rate of growth of said host cell in the pres-
ence of said compound is indicative of a cancer
therapeutic.
The challenged claims thus relate to isolated gene se-
quences and diagnostic methods of identifying mutations
in these sequences. To place this suit in context, we take
a step back to provide background on the science involved,
including the identification of the BRCA genes, and the
Plaintiffs’ connections to the invention and to Myriad.
I.
Human genetics is the study of heredity in human be-
ings. 1 The human genome, the entirety of human genetic
information, contains approximately 25,000 genes, which
form the basis of human inheritance. The majority of
genes act by specifying polypeptide chains that form
1 The district court’s opinion, SJ Op., at 192-203,
contains a detailed and comprehensive discussion of the
science involved in this case. We repeat only the basics
here.
ASSOCIATION FOR MOLECULAR v. PTO 12
proteins. Proteins in turn make up living matter and
catalyze all cellular processes.
Chemically, the human genome is composed of deoxy-
ribonucleic acid (“DNA”). Each DNA molecule is made up
of repeating units of four nucleotide bases—adenine (“A”),
thymine (“T”), cytosine (“C”), and guanine (“G”)—which
are covalently linked, or bonded, 2 together via a sugar-
phosphate, or phosphodiester, backbone. DNA generally
exists as two DNA strands intertwined as a double helix
in which each base on a strand pairs, or hybridizes, with a
complementary base on the other strand: A pairs with T,
and C with G. Figure 1 below depicts the structure of a
DNA double helix and the complementary pairing of the
four nucleotide bases, represented by A, T, C, and G.
Figure 1
The linear order of nucleotide bases in a DNA mole-
cule is referred to as its “sequence.” The sequence of a
gene is thus denoted by a linear sequence of As, Ts, Gs,
and Cs. “DNA sequencing” or “gene sequencing” refers to
the process by which the precise linear order of nucleo-
tides in a DNA segment or gene is determined. A gene’s
nucleotide sequence in turn encodes for a linear sequence
of amino acids that comprise the protein encoded by the
2 Covalent bonds are chemical bonds characterized
by the sharing of electrons between atoms in a molecule.
13 ASSOCIATION FOR MOLECULAR v. PTO
gene, e.g., the BRCA1 gene encodes for the BRCA1 pro-
tein. Most genes have both “exon” and “intron” se-
quences. Exons are DNA segments that are necessary for
the creation of a protein, i.e., that code for a protein.
Introns are segments of DNA interspersed between the
exons that, unlike exons, do not code for a protein.
The creation of a protein from a gene comprises two
steps: transcription and translation. First, the gene
sequence is “transcribed” into a different nucleic acid
called ribonucleic acid (“RNA”). RNA has a chemically
different sugar-phosphate backbone than DNA, and it
utilizes the nucleotide base uracil (“U”) in place of
thymine (“T”). For transcription, the DNA double helix is
unwound and each nucleotide on the non-coding, or tem-
plate, DNA strand is used to make a complementary RNA
molecule of the coding DNA strand, i.e., adenine on the
template DNA strand results in uracil in the RNA mole-
cule, thymine results in adenine, guanine in cytosine, and
cytosine in guanine. The resulting “pre-RNA,” like the
DNA from which it was generated, contains both exon and
intron sequences. Next, the introns are physically excised
from the pre-RNA molecule, in a process called “splicing,”
to produce a messenger RNA (“mRNA”). Figure 2 below
shows the steps of transcribing a gene that contains three
exons (exon 1-3) and two introns (intron 1 and 2) into a
pre-RNA, followed by RNA splicing of the introns to
produce an mRNA containing just the exon sequences.
ASSOCIATION FOR MOLECULAR v. PTO 14
Figure 2
Following transcription, the resulting mRNA is
“translated” into the encoded protein. Genes, and their
corresponding mRNAs, encode proteins via three-
nucleotide combinations called codons. Each codon corre-
sponds to one of the twenty amino acids that make up all
proteins or a “stop” signal that terminates protein trans-
lation. For example, the codon adenine-thymine-guanine
(ATG, or UTG in the corresponding mRNA), encodes the
amino acid methionine. The relationship between the
sixty-four possible codon sequences and their correspond-
ing amino acids is known as the genetic code. Figure 3
below represents an mRNA molecule that translates into
a protein of six amino acids (Codon 1, AUG, methionine;
Codon 2, ACG, threonine; Codon 3, GAG, glutamic acid;
Codon 4, CUU, leucine; Codon 5, CGG, arginine; Codon 6,
AGC, serine), and ends with one of the three stop codons,
UAG.
15 ASSOCIATION FOR MOLECULAR v. PTO
Figure 3
Changes, or mutations, in the sequence of a human
gene can alter the structure as well as the function of the
resulting protein. Small-scale changes include point
mutations in which a change to a single nucleotide alters
a single amino acid in the encoded protein. For example,
a base change in the codon GCU to CGU changes an
alanine in the encoded protein to an arginine. Larger
scale variations include the deletion, rearrangement, or
duplication of larger DNA segments, ranging from several
hundreds to over a million nucleotides, and result in the
elimination, misplacement, or duplication of an entire
gene or genes. While some mutations have little or no
effect on the body’s processes, others result in disease, or
an increased risk of developing a particular disease. DNA
sequencing is used in clinical diagnostic testing to deter-
mine whether a gene contains mutations associated with
a particular disease or risk of a particular disease.
Nearly every cell in the human body contains an indi-
vidual’s entire genome. DNA in the cell, called “native” or
“genomic” DNA, is packaged into twenty-three pairs of
chromosomes. Chromosomes are complex structures of a
ASSOCIATION FOR MOLECULAR v. PTO 16
single DNA molecule wrapped around proteins called
histones, as shown in Figure 4 below.
Figure 4
Humans have twenty-two pairs of autosomal chromo-
somes, numbered one to twenty-two according to size from
largest to smallest, and one pair of sex chromosomes, two
X chromosomes in females and one X and one Y chromo-
some in males.
Genomic DNA can be extracted from its cellular envi-
ronment using a number of well-established laboratory
techniques. A particular segment of DNA, such as a gene,
can then be excised or amplified from the DNA to obtain
the isolated DNA segment of interest. DNA molecules
can also be synthesized in the laboratory. One type of
synthetic DNA molecule is complementary DNA
(“cDNA”). cDNA is synthesized from mRNA using com-
17 ASSOCIATION FOR MOLECULAR v. PTO
plementary base pairing in a manner analogous to RNA
transcription. The process results in a double-stranded
DNA molecule with a sequence corresponding to the
sequence of an mRNA produced by the body. Because it is
synthesized from mRNA, cDNA contains only the exon
sequences, and thus none of the intron sequences, from a
native gene sequence.
II.
Mutations in the BRCA genes correlate with an in-
creased risk of breast and ovarian cancer. The average
woman in the United States has around a twelve to
thirteen percent risk of developing breast cancer in her
lifetime. Women with BRCA mutations, in contrast, face
a cumulative risk of between fifty to eighty percent of
developing breast cancer and a cumulative risk of ovarian
cancer of between twenty to fifty percent. Diagnostic
genetic testing for the existence of BRCA mutations is
therefore an important consideration in the provision of
clinical care for breast or ovarian cancer. This testing
provides a patient with information on her risk for heredi-
tary breast and ovarian cancers, and thus aids in the
difficult decision regarding whether to undertake preven-
tive options, including prophylactic surgery. Diagnostic
results can also be an important factor in structuring an
appropriate course of cancer treatment, since certain
forms of chemotherapy are more effective in treating
cancers related to BRCA mutations.
The inventors of the patents in suit identified the ge-
netic basis of BRCA1 and BRCA2-related cancers using
an analysis called positional cloning. Relying on a large
set of DNA samples from families with inherited breast
and ovarian cancers, the inventors correlated the occur-
rence of cancer in individual family members with the
inheritance of certain marker DNA sequences. This
ASSOCIATION FOR MOLECULAR v. PTO 18
allowed the inventors to identify, or “map,” the physical
location of the BRCA genes within the human genome
and to isolate the BRCA genes and determine their exact
nucleotide sequences. This in turn allowed Myriad to
provide BRCA diagnostic testing services to women.
Myriad filed the first patent application leading to the
patents in suit covering isolated BRCA1 DNA and associ-
ated diagnostic methods in August 1994. The first patent,
the ’473 patent, issued on December 2, 1997. Myriad filed
the first application leading to the patents in suit covering
isolated BRCA2 DNA and associated diagnostic methods
in December 1995, and the first patent, the ’492 patent,
issued on November 17, 1998.
III.
Myriad, however, was not the only entity to imple-
ment clinical BRCA testing services. Starting in 1996,
the University of Pennsylvania’s Genetic Diagnostic
Laboratory (“GDL”), co-directed by plaintiffs Haig H.
Kazazian, Jr., M.D. and Arupa Ganguly, Ph.D., provided
BRCA1/2 diagnostic services to women. By 1999, how-
ever, accusations by Myriad that GDL’s BRCA testing
services infringed its patents forced the lab to stop provid-
ing such services.
The first sign of a dispute came in early 1998. At that
time, Dr. Kazazian recalls a dinner with Dr. Mark Skol-
nick, inventor and Chief Science Office at Myriad. At the
dinner, Skolnick informed Kazazian that Myriad was
planning to stop GDL from providing clinical BRCA
testing in light of Myriad’s patents. A month or two later,
in May 1998, Kazazian received a letter from William A.
Hockett, Director of Corporate Communications at Myr-
iad. The letter stated that Myriad knew that Kazazian
was currently providing BRCA1 diagnostic testing ser-
vices, and that Myriad, as patent holder of five U.S.
19 ASSOCIATION FOR MOLECULAR v. PTO
patents covering the isolated BRCA1 gene and diagnostic
testing, was making available to select institutions a
collaborative license. Attached to the letter was a copy of
Myriad’s collaborative agreement, which proposed se-
verely limiting GDL’s testing services to certain tests for
patients of Ashkenazi Jewish descent. Plaintiff Harry
Ostrer, M.D, a researcher at New York University
(“NYU”) School of Medicine, received the same letter and
collaborative agreement in May 1998, although his labo-
ratory did not, at the time, provide such testing services.
Rather, Ostrer sent patient samples to GDL for BRCA
genetic testing.
Months later, in August 1998, Dr. Kazazian received a
second letter, this time from George A. Riley of the law
firm O’Melveny & Myers LLP. The letter identified by
number five Myriad patents “covering, among other
things, the BRCA1 gene sequence . . . and methods for
detecting alternations in the BRCA1 sequence.” J.A.
1145. The letter also indicated that it “has come to Myr-
iad’s attention that you are engaged in commercial testing
activities that infringe Myriad’s patents,” and that
“[u]nless and until a licensing arrangement is completed
. . . you should cease all infringing testing activity.” Id.The letter noted, however, that the cease-and-desist
notification did not apply to research testing “for the
purpose of furthering non-commercial research programs,
the results of which are not provided to the patient and
for which no money is received from the patient or the
patient’s insurance.” Id.In June 1999, Robert Terrell, the General Counsel for
University of Pennsylvania, received a similar cease-and-
desist letter from Christopher Wight, Myriad’s General
Counsel. The letter stated, “It has come to our attention
that Dr. Haig H. Kazazian, Jr. of the University of Penn-
sylvania is continuing to willfully engage in commercial
ASSOCIATION FOR MOLECULAR v. PTO 20
BRCA1 and BRCA2 genetic testing activities, in violation
of the University of Pennsylvania’s previous assurances
that such commercial testing activities would be discon-
tinued.” J.A. 2890. Terrell responded to Wight by letter
on September 10, 1999, stating that “the University
agrees that it will not accept samples for BRCA1 research
testing from third parties.” J.A. 2891. Kazazian thus
informed Dr. Ostrer that GDL would no longer be accept-
ing patient samples for BRCA testing from him or anyone
else as a result of the patent infringement assertions
made by Myriad. As a result, Ostrer started sending
patient samples for BRCA genetic testing to Myriad, who
became (and remains today) the only provider of such
services in the United States.
During this period, Myriad also initiated several pat-
ent infringement suits against entities providing clinical
BRCA testing. Myriad filed suit against Oncormed Inc. in
1997 and again in 1998, Myriad Genetics v. Oncormed,
Nos. 2:97-cv-922, 2:98-cv-35 (D. Utah), and the University
of Pennsylvania in 1998, Myriad Genetics v. Univ. of Pa.,
No. 2:98-cv-829 (D. Utah). Both lawsuits were later
dismissed without prejudice after each defendant agreed
to discontinue all allegedly infringing activity.
None of the plaintiffs besides Drs. Kazazian, Ganguly,
and Ostrer, allege that Myriad directed any letters or
other communications regarding its patents at them.
Rather, the other researchers and medical organization
members state simply that knowledge of Myriad’s vigor-
ous enforcement of its patent rights against others
stopped them from engaging in clinical BRCA genetic
testing, although they have the personnel, expertise, and
facilities as well as the desire to provide such testing. The
patient plaintiffs state that they have been unable to
obtain any BRCA genetic testing or their desired BRCA
21 ASSOCIATION FOR MOLECULAR v. PTO
testing, either through their insurance or at a price that
they can afford, because of Myriad’s patent protection.
Like the other researchers, Dr. Kazazian states that if
Myriad’s patents were held invalid, he and Dr. Ganguly
would be able to resume BRCA testing within a matter of
a few weeks. He notes, however, that this is only if they
“decided to resume BRCA testing.” J.A. 2852. Ganguly
concurs, stating that if the patents were invalidated, “I
would immediately consider resuming BRCA testing in
my laboratory.” J.A. 2892. Ostrer also indicates that his
lab has all the personnel, facilities, and expertise neces-
sary to undertake clinical BRCA testing and emphatically
states that his lab “would immediately begin to perform
BRCA1/2-related genetic testing upon invalidation of the
Myriad patents.” J.A. 2936-38.
IV.
After Plaintiffs filed suit, Myriad moved to have the
case dismissed, alleging that the Plaintiffs lacked stand-
ing to bring a declaratory judgment suit challenging the
validity of its patents. The district court disagreed,
however, holding that the Plaintiffs had established
Article III standing under the “all the circumstances” test
articulated by the Supreme Court in MedImmune, Inc. v.
Genentech, Inc., 549 U.S. 118, 127 (2007). DJ Op., at 385-
92. The court first found that Myriad had engaged in
sufficient “affirmative acts” based on the company’s
assertion of its “right to preclude others from engaging in
BRCA1/2 genetic testing through personal communica-
tions, cease-and-desist letters, licensing offers, and litiga-
tion,” the result of which was “the widespread
understanding that one may engage in BRCA1/2 testing
at the risk of being sued for infringement liability by
Myriad.” Id. at 390. Myriad’s actions, the court con-
cluded, had placed “the Plaintiffs in precisely the situa-
ASSOCIATION FOR MOLECULAR v. PTO 22
tion that the Declaratory Judgment Act was designed to
address: the Plaintiffs have the ability and desire to
engage in BRCA1/2 testing as well as the belief that such
testing is within their rights, but cannot do so without
risking infringement liability.” Id.
In so holding, the court rejected Myriad’s argument
that there must be some act directed toward the Plain-
tiffs, noting that Myriad had, in fact, taken affirmative
acts toward plaintiffs Dr. Kazazian and Dr. Ganguly. Id.
at 387-88. The court also rejected Myriad’s arguments
that the cease-and-desist letter sent to plaintiff Kazazian
was too old to support declaratory judgment jurisdiction
and that the legal actions brought against third parties
could not be considered in the jurisdictional analysis. Id.
at 388-89. The court concluded that rigid adherence to
either of these requirements would be inconsistent with
MedImmune’s mandate that the court assess the facts
alleged under all the circumstances. Id.
The district court also found that the Plaintiffs had al-
leged sufficient meaningful preparations for infringement
to establish declaratory judgment jurisdiction. Id. at 390-
92. With respect to the researchers, the court held it was
sufficient that they were all “ready, willing, and able” to
begin BRCA1/2 testing within the normal course of their
laboratories’ research, rejecting Myriad’s argument that
they needed to allege specific preparatory activities. Id.
at 390-91. The court also rejected Myriad’s argument
that plaintiffs Kazazian and Ganguly testified only that
they would “consider” engaging in allegedly infringing
activities, concluding that the proper focus of the inquiry
is whether they are meaningfully prepared, not whether
they have made a final, conclusive decision to engage in
such activities. Id. at 391 n.18.
23 ASSOCIATION FOR MOLECULAR v. PTO
The parties then moved for summary judgment on the
merits of Plaintiffs’ § 101 challenge to Myriad’s patent
claims. The district court held for Plaintiffs, concluding
that the fifteen challenged claims were drawn to non-
patentable subject matter and thus invalid under § 101.
SJ Op., at 220-37. Regarding the composition claims, the
court held that isolated DNA molecules fall within the
judicially created “products of nature” exception to § 101
because such isolated DNAs are not “markedly different”
from native DNAs. Id. at 222, 232 (quoting Diamond v.
Chakrabarty, 447 U.S. 303 (1980)). The court relied on
the fact that, unlike other biological molecules, DNAs are
the “physical embodiment of information,” and that this
information is not only preserved in the claimed isolated
DNA molecules, but also essential to their utility as
molecular tools. Id. at 228-32.
Turning to the method claims, the court held them
patent ineligible under this court’s then definitive ma-
chine-or-transformation test. Id. at 233 (citing In re
Bilski, 545 F.3d 943 (Fed. Cir. 2008), affirmed on other
grounds by Bilski v. Kappos, 130 S. Ct. 3218, 3225 (2010)).
The court held that the claims covered “analyzing” or
“comparing” DNA sequences by any method, and thus
covered mental processes independent of any physical
transformations. Id. at 233-35. In so holding, the court
distinguished Myriad’s claims from those at issue in
Prometheus based on the “determining” step in the latter
being construed to include the extraction and measure-
ment of metabolite levels from a patient sample. SJ Op.,
at 234-35 (citing Prometheus Labs., Inc. v. Mayo Collabo-
rative Servs., 628 F.3d 1347, 1350 (Fed. Cir. 2010), cert.
granted 2011 WL 973139 (June 20, 2011)). Alternatively,
the court continued, even if the claims could be read to
include the transformations associated with isolating and
sequencing human DNA, these transformations would
ASSOCIATION FOR MOLECULAR v. PTO 24
constitute no more than preparatory data-gathering steps.
Id. at 236 (citing In re Grams, 888 F.2d 835, 840 (Fed. Cir.
1989)). Finally, the court held that the one method claim
to “comparing” the growth rate of cells claimed a basic
scientific principle and that the transformative steps
amounted to only preparatory data gathering. Id. at 237.
Myriad appealed. We have jurisdiction pursuant to
28 U.S.C. § 1295(a)(1).
DISCUSSION
I. Declaratory Judgment Jurisdiction
A.
The first question we must address is whether the
district court correctly exercised declaratory judgment
jurisdiction over this suit. The Declaratory Judgment Act
provides that, “In a case of actual controversy within its
jurisdiction . . . any court of the United States . . . may
declare the rights and other legal relations of any inter-
ested party seeking such declaration, whether or not
further relief is or could be sought.” 28 U.S.C. § 2201(a).
The phrase “a case of actual controversy” in the Act refers
to the types of “cases” and “controversies” that are justici-
able under Article III of the U.S. Constitution. Aetna Life
Ins. v. Haworth, 300 U.S. 227, 239-40 (1937).
Although no bright-line rule exists for determining
whether a declaratory judgment action satisfies Article
III’s case-or-controversy requirement, the Supreme Court
has held that the dispute must be “definite and concrete,
touching the legal relations of parties having adverse
legal interests,” “real and substantial,” and “admi[t] of
specific relief through a decree of a conclusive character,
as distinguished from an opinion advising what the law
would be upon a hypothetical state of facts.” MedIm-
mune, 549 U.S. at 127 (quoting Aetna Life, 300 U.S. at25 ASSOCIATION FOR MOLECULAR v. PTO
240-41). “Basically, the question in each case is whether
the facts alleged, under all the circumstances, show that
there is a substantial controversy, between parties having
adverse legal interests, of sufficient immediacy and
reality to warrant the issuance of a declaratory judg-
ment.” Id. (quoting Md. Cas. Co. v. P. Coal & Oil Co., 312
U.S. 270, 273 (1941)).
In applying MedImmune’s all-the-circumstances test
to a declaratory judgment action, we are guided by the
Supreme Court’s three-part framework for determining
whether an action presents a justiciable Article III con-
troversy: standing, ripeness, and mootness. See Caraco
Pharm. Labs., Ltd. v. Forest Labs., Inc., 527 F.3d 1278,
1291 (Fed. Cir. 2008). In this case, the parties have
framed the jurisdictional issue as one of standing. See
MedImmune, 549 U.S. at 128 n.8. (“The justiciability
problem that arises, when the party seeking declaratory
relief is himself preventing the complained-of injury from
occurring, can be described in terms of standing . . . or . . .
ripeness.” (internal citations omitted)).
“[T]he irreducible constitutional minimum of standing
contains three elements.” Lujan v. Defenders of Wildlife,
504 U.S. 555, 560 (1992). “First, the plaintiff must have
suffered an injury in fact—an invasion of a legally pro-
tected interest which is (a) concrete and particularized,
and (b) actual or imminent, not conjectural or hypotheti-
cal.” Id. (internal citations and quotations omitted).
“Second, there must be a causal connection between the
injury and the conduct complained of–the injury has to be
‘fairly . . . trace[able] to the challenged action of the
defendant . . . .’” Id. (quoting Simon v. E. Ky. Welfare
Rights Org., 426 U.S. 26, 41-42 (1976)). “Third, it must be
‘likely,’ as opposed to merely ‘speculative,’ that the injury
will be ‘redressed by a favorable decision.’” Id. at 561
(quoting Simon, 426 U.S. at 38, 43).
ASSOCIATION FOR MOLECULAR v. PTO 26
“Whether an actual case or controversy exists so that
a district court may entertain an action for a declaratory
judgment of non-infringement and/or invalidity is gov-
erned by Federal Circuit law.” MedImmune, Inc. v. Cen-
tocor, Inc., 409 F.3d 1376, 1378 (Fed. Cir. 2005), overruled
on other grounds, MedImmune, 549 U.S. at 130-31.
Following MedImmune, this court has held that, to estab-
lish an injury in fact traceable to the patentee, a declara-
tory judgment plaintiff must allege both (1) an affirmative
act by the patentee related to the enforcement of his
patent rights, SanDisk Corp. v. STMicroelecs., Inc., 480
F.3d 1372, 1380-81 (Fed. Cir. 2007), and (2) meaningful
preparation to conduct potentially infringing activity, Cat
Tech LLC v. TubeMaster, Inc., 528 F.3d 871, 880 (Fed.
Cir. 2008). We review the exercise of declaratory judg-
ment jurisdiction upon a particular set of facts de novo.
SanDisk Corp., 480 F.3d at 1377.
B.
Myriad challenges the district court’s jurisdictional
decision on the grounds that Myriad and the Plaintiffs do
not have adverse legal interests and that Plaintiffs have
failed to allege a controversy of sufficient immediacy and
reality to warrant the issuance of a declaratory judgment.
Specifically, Myriad argues that Plaintiffs have failed to
allege any “affirmative acts” by Myriad within the past
ten years relating to the patents in suit or directed at any
Plaintiff. According to Myriad, the district court erred by
relying on “stale communications” directed at Drs. Ka-
zazian, Ganguly, and Ostrer over a decade ago, as well as
ten-year-old licensing and litigation activities directed at
third parties, and thus exercised jurisdiction based solely
on Plaintiffs’ subjective fear of suit, arising from rumor
and innuendo in the research community.
27 ASSOCIATION FOR MOLECULAR v. PTO
Plaintiffs respond that they have standing under
MedImmune’s all-the-circumstances test because, not only
are they undisputedly prepared to immediately undertake
potentially infringing activities, but also Myriad took
sufficient affirmative acts with respect to the patents in
suit. Regarding the latter, Plaintiffs assert that Myriad
sued, threatened to sue, or demanded license agreements
from every known institution offering BRCA clinical
testing, including university labs directed by plaintiffs
Kazazian, Ganguly, and Ostrer, forcing each to cease such
testing. And, according to Plaintiffs, the awareness of
Myriad’s vigorous assertion of its patent rights still con-
tinues to suppress their ability to perform clinical BRCA
testing, placing Plaintiffs in the very dilemma the De-
claratory Judgment Act was intended to address: they
must either proceed with BRCA-related activities and risk
liability for patent infringement, or refrain from such
activities despite believing Myriad’s patents are invalid.
Under the facts alleged in this case, we conclude that
one Plaintiff, Dr. Ostrer, has established standing to
maintain this declaratory judgment suit. All Plaintiffs
claim standing under the Declaratory Judgment Act
based on the same alleged injury: that they cannot un-
dertake the BRCA-related activities that they desire
because of Myriad’s enforcement of its patent rights
covering BRCA1/2. 3 Only three plaintiffs, however,
3 Certain patients also allege an injury based on
their inability to gain access to affordable BRCA genetic
testing because of Myriad’s patent dominance of such
services. While denial of health services can, in certain
circumstances, state a judicially cognizable injury, see
Simon, 426 U.S. at 40-41, Plaintiffs have not pressed this
as an independent ground for standing. Moreover, we fail
to see how the inability to afford a patented invention
could establish an invasion of a legally protected interest
for purposes of standing.
ASSOCIATION FOR MOLECULAR v. PTO 28
allege an injury traceable to Myriad; only Drs. Kazazian,
Ganguly, and Ostrer allege affirmative patent enforce-
ment actions directed at them by Myriad. Of these three,
Dr. Ostrer clearly alleges a sufficiently real and imminent
injury because he alleges an intention to actually and
immediately engage in allegedly infringing BRCA-related
activities. We address each in turn.
Although MedImmune relaxed this court’s more re-
strictive “reasonable apprehension of suit” test for de-
claratory judgment jurisdiction, SanDisk, 480 F.3d at
1380, it did not alter “the bedrock rule that a case or
controversy must be based on a real and immediate injury
or threat of future injury that is caused by the defen-
dants,” Prasco, LLC v. Medicis Pharm. Corp., 537 F.3d
1329, 1339 (Fed. Cir. 2008). Accordingly, following
MedImmune, this court has continued to hold that de-
claratory judgment jurisdiction will not arise merely on
the basis that a party learns of the existence of an ad-
versely held patent, or even perceives that such a patent
poses a risk of infringement, in the absence of some
affirmative act by the patentee. SanDisk, 480 F.3d at
1380-81. Thus, without defining the outer boundaries of
declaratory judgment jurisdiction, we have held that
“where a patentee asserts rights under a patent based on
certain identified ongoing or planned activity of another
party, and where that party contends that it has the right
to engage in the accused activity without license, an
Article III case or controversy will arise . . . .” Id. at 1381;
see also Prasco, 537 F.3d at 1338 (“A patentee can cause
. . . an injury [sufficient to create an actual controversy] in
a variety of ways, for example, by creating a reasonable
apprehension of an infringement suit, [or] demanding the
right to royalty payments.” (internal citations omitted)).
In this case, Myriad demanded a royalty under its
patents from Dr. Ostrer based on his clinical BRCA-
29 ASSOCIATION FOR MOLECULAR v. PTO
related activities. In May 1998, Myriad’s Director of
Corporate Communications sent Ostrer a letter proposing
a collaborative license. The letter stated that Myriad was
aware that Ostrer was either currently providing, or was
interested in initiating, BRCA1 diagnostic testing services
and that Myriad, as holder of U.S. patents covering the
BRCA1 gene and diagnostic testing of BRCA1, was mak-
ing available to his institution, NYU Medical Center, a
limited collaborative license. The collaborative license
required NYU to make a payment to Myriad for each non-
research BRCA test performed.
At the same time, as Ostrer was aware, Myriad was
asserting its patent rights against other similarly situated
parties, a fact to be considered in assessing the existence
of an actual controversy under the totality of circum-
stances. See Micron Tech., Inc. v. Mosaid Techs., Inc., 518
F.3d 897, 901 (Fed. Cir. 2008). Soon after Ostrer received
Myriad’s letter, Dr. Kazazian informed him that, because
of Myriad’s assertion of its patent rights against him,
GDL would no longer be accepting patient samples for
BRCA genetic testing. Myriad’s assertion of its patent
rights against Kazazian escalated into a patent infringe-
ment suit by Myriad against the University of Pennsyl-
vania, which was later dismissed without prejudice after
the University agreed to cease all accused BRCA testing
services. Myriad also sued Oncormed for patent in-
fringement based on its BRCA genetic testing services.
As a result of Myriad’s patent enforcement actions, Dr.
Ostrer was forced to send all patient samples to Myriad,
now the sole provider of BRCA diagnostic testing services.
Dr. Ostrer, on the other hand, maintains that he could
have proceeded with his BRCA-related clinical activities
without taking a license from Myriad. This assertion is
based on his belief that the patents Myriad claims cover
such activities are invalid because genes are patent-
ASSOCIATION FOR MOLECULAR v. PTO 30
ineligible products of nature. Acting on his belief, Ostrer
seeks in this lawsuit a declaration of his right to under-
take BRCA-related clinical activities without a license.
Accordingly, Myriad and Dr. Ostrer have taken adverse
legal positions regarding whether or not Ostrer can en-
gage in BRCA genetic testing without infringing any valid
claim to “isolated” BRCA DNAs or methods of “analyzing”
or “comparing” BRCA sequences, as recited in Myriad’s
patents. See Aetna Life, 300 U.S. at 242 (holding declara-
tory judgment jurisdiction existed when “the parties had
taken adverse positions with respect to their existing
obligations” on an insurance contract).
Dr. Ostrer has also alleged a controversy of sufficient
reality and immediacy, MedImmune, 549 U.S. at 127; he
has alleged a concrete and actual injury traceable to
Myriad’s assertion of its patent rights, see Lujan, 504 U.S.
at 560. First, Ostrer seeks to undertake specific BRCA-
related activities—BRCA diagnostic testing—for which
Myriad has demanded a license under specific patents—
those that cover the isolated BRCA genes and BRCA
diagnostic testing. Thus, Ostrer does not request “an
opinion advising what the law would be upon a hypotheti-
cal state of facts,” Aetna Life, 300 U.S. at 241, but rather
whether his proposed BRCA testing services are covered
by valid patent claims to “isolated” BRCA genes and
methods of “comparing” the genes’ sequences. Second,
Ostrer not only has the resources and expertise to imme-
diately undertake clinical BRCA testing, but also states
unequivocally that he will immediately begin such test-
ing. In contrast to Ostrer, who alleges an actual and
imminent injury for purposes of standing, Drs. Kazazian
and Ganguly allege only that they will “consider” resum-
ing BRCA testing. These “‘some day’ intentions” are
insufficient to support an “actual or imminent” injury for
standing “without . . . any specification of when the some
31 ASSOCIATION FOR MOLECULAR v. PTO
day will be.” Lujan, 504 U.S. at 564. As a result, Drs.
Kazazian and Ganguly do not have standing.
Myriad seeks to escape this result based on the timing
of its enforcement actions. Specifically, Myriad argues
that time has extinguished the immediacy and reality of
any controversy, relying on language that hearkens back
to our pre-MedImmune reasonable apprehension of suit
test. See, e.g., Appellant Br. 26 (“[A] patentee’s ten-year
silence presumptively extinguishes any reasonable objec-
tive fear of suit.”). We disagree. In many cases a contro-
versy made manifest by a patentee’s affirmative assertion
of its patent rights will dissipate as market players and
products change. In this case, however, the relevant
circumstances surrounding Myriad’s assertion of its
patent rights have not changed despite the passage of
time. 4
Myriad’s active enforcement of its patent rights forced
Dr. Ostrer, as well as every other similarly situated
researcher and institution, to cease performing the chal-
lenged BRCA testing services, leaving Myriad as the sole
provider of BRCA clinical testing to patients in the United
States. Since that time, neither the accused activities nor
the parties’ positions have changed. First, Myriad does
not allege that genetic testing technology has changed in
any way that renders its past assertions of its patent
rights irrelevant to Ostrer’s currently proposed BRCA
testing. Rather, the patents cover, as Myriad asserted in
the late 1990s, the basic components of any such test: the
4 Myriad’s analogy to laches is also unconvincing.
Laches bars the recovery of pre-filing damages; it does not
preclude a patent action for prospective relief, the type of
relief sought here. See A.C. Aukerman Co. v. R.L. Chaides
Const. Co., 960 F.2d 1020, 1041 (Fed. Cir. 1992) (en banc)
(“[L]aches bars relief on a patentee’s claim only with
respect to damages accrued prior to suit.”).
ASSOCIATION FOR MOLECULAR v. PTO 32
isolated BRCA genes and the diagnostic step of comparing
the genes’ sequences.
Second, ever since Myriad’s enforcement efforts elimi-
nated all competition, Myriad and Ostrer have not altered
their respective positions. Ostrer, still laboring under
Myriad’s threat of infringement liability, has not at-
tempted to provide BRCA testing; yet, as a researcher, he
remains in the same position with respect to his ability
and his desire to provide BRCA testing as in the late
1990s. Furthermore, nothing in the record suggests that
any researcher or institution has successfully attempted
to compete with Myriad, or that Myriad has in any way
changed its position with regard to its patent rights. Just
as active enforcement of one’s patent rights against others
can maintain a real and immediate controversy despite
the passage of time, see Micron, 518 F.3d at 901, so too
can the successful assertion of such rights when the
relevant circumstances remain unchanged. Thus, consis-
tent with the purpose of the Declaratory Judgment Act,
Ostrer need not risk liability and treble damages for
patent infringement before seeking a declaration of his
contested legal rights. See MedImmune, 549 U.S. at 134.
Myriad also argues that the record refutes Ostrer’s
claim that he has been restrained from engaging in
BRCA-related gene sequencing. Specifically, Myriad
argues that since Myriad published its discoveries of the
BRCA1 and BRCA2 genes in October 1994 and March
1996, respectively, over 18,000 scientists have conducted
research on the BRCA genes and over 8,600 research
papers have been published. Furthermore, according to
Myriad, plaintiff Wendy Chung concedes that her lab
currently conducts sequencing of BRCA genes. Yet, both
Drs. Chung and Ostrer state that, although they conduct
gene sequencing, they are forbidden from informing their
research subjects of the results of their BRCA tests with-
33 ASSOCIATION FOR MOLECULAR v. PTO
out first sending the samples to Myriad. Accordingly,
Ostrer is restrained from the BRCA-related activity that
he desires to undertake: clinical diagnostic testing.
Myriad’s communications with Dr. Ostrer confirm this
understanding. The licensing letter Myriad sent to Ostrer
proposed a collaborative agreement giving NYU the right
to perform “Research Tests” without payment to Myriad.
J.A. 2967. “Research Tests” are defined as tests that
further “non-commercial research programs, the results of
which are not provided to the patient and for which no
money is received.” J.A. 2965 (emphasis added). In
contrast, the agreement requires payment to Myriad for
each “Testing Service” performed, with “Testing Services”
defined as “medical laboratory testing . . . for the presence
or absence of BRCA1 mutations for the purpose of deter-
mining or predicting predisposition to, or assessing the
risk of breast or ovarian cancer in humans.” J.A. 2966-67.
Thus, Myriad’s patent enforcement actions never targeted
the non-clinical BRCA research now cited by Myriad, and
Ostrer’s ability to perform such research does not address
the injury asserted here.
Finally, Myriad argued in its reply brief and at oral
argument that Plaintiffs’ declaratory action will not afford
them the relief they want, a requirement for standing.
Lujan, 504 U.S. at 560-61; see also MedImmune, 549 U.S.
at 127 n.7 (“[A] litigant may not use a declaratory-
judgment action to obtain piecemeal adjudication of
defenses that would not finally and conclusively resolve
the underlying controversy.”). Specifically, Myriad as-
serts that because Plaintiffs have challenged just fifteen
composition and method claims, while admitting that
other unchallenged claims to BRCA probes and primers
will still prevent them from engaging in BRCA sequenc-
ing, a favorable decision will not redress the Plaintiffs’
alleged injury. Again, we disagree.
ASSOCIATION FOR MOLECULAR v. PTO 34
The Supreme Court has required only that it is
“likely,” rather than “merely ‘speculative,’” that the al-
leged injury will be “redressed by a favorable decision.”
Lujan, 504 U.S. at 561. The Court has not required
certainty. For example, in Village of Arlington Heights v.
Metropolitan Housing Development Corp., the Court held
that the plaintiffs had standing to challenge a suburb’s
exclusionary zoning ordinance, as the ordinance stood as
“an absolute barrier” to the housing development Metro-
politan Housing Development Corp. (“MHDC”) had con-
tracted to provide in the village. 429 U.S. 252, 261 (1977).
The Court noted that injunctive relief, while removing the
“barrier” of the ordinance, would not “guarantee” that the
housing would be built since MHDC still had to secure
financing, qualify for federal subsidies, and carry through
with construction. Id. The Court nevertheless recognized
that “all housing developments are subject to some extent
to similar uncertainties,” and concluded that it was suffi-
cient that there was a “substantial probability” that the
housing development would be built. Id. at 261, 264.
In this case, Myriad’s challenged composition and
method claims undisputedly provide “an absolute barrier”
to Dr. Ostrer’s ability to undertake BRCA diagnostic
testing activities, and a declaration of those claims’ inva-
lidity would remove that barrier. See id. at 261. More-
over, while there may be other patent claims directed to
BRCA probes and primers that prevent Ostrer from
performing BRCA diagnostic testing free of infringement
liability, Myriad has failed to direct us to any specific
unchallenged claim that will have that effect. And Plain-
tiffs’ counsel stated at oral argument that his clients can
sequence the BRCA genes without using BRCA probes
and primers. Oral Arg. at 34:07-25, 34:53-35:29 available
at http://www.cafc.uscourts.gov/oral-argument-
recordings/2010-1406/all. Accordingly, we decline to
35 ASSOCIATION FOR MOLECULAR v. PTO
construe claims and hold on this record that Dr. Ostrer’s
proposed BRCA-related activities would infringe unchal-
lenged claims to primers and probes. We thus conclude
that it is likely, not merely speculative, that Dr. Ostrer’s
injury will be redressed by a favorable decision.
Accordingly, although we affirm the district court’s
decision to exercise declaratory judgment jurisdiction, we
affirm on much narrower grounds. The district court
failed to limit its jurisdictional holding to affirmative acts
by the patentee directed at specific Plaintiffs, see San-
Disk, 480 F.3d at 1380-81, erroneously holding all the
Plaintiffs had standing based on “the widespread under-
standing that one may engage in BRCA1/2 testing at the
risk of being sued for infringement liability by Myriad,”
DJ Op., at 390. We disagree, and thus we reverse the
district court’s holding that the various plaintiffs other
than Dr. Ostrer have standing to maintain this declara-
tory judgment action. Simply disagreeing with the exis-
tence of a patent or even suffering an attenuated, non-
proximate, effect from the existence of a patent does not
meet the Supreme Court’s requirement for an adverse
legal controversy of sufficient immediacy and reality to
warrant the issuance of a declaratory judgment. See
MedImmune, 549 U.S. at 127.
Having found one plaintiff with standing to maintain
this declaratory judgment action, see Horne v. Flores, 129
S. Ct. 2579, 2592-93 (2009), we may turn now to the
merits of Myriad’s appeal of the district court’s summary
judgment decision, which held all fifteen challenged
composition and method claims invalid under § 101.
II. Patentable Subject Matter
Under the Patent Act, “Whoever invents or discovers
any new and useful process, machine, manufacture, or
composition of matter, or any new and useful improve-
ASSOCIATION FOR MOLECULAR v. PTO 36
ment thereof, may obtain a patent therefor, subject to the
conditions and requirements of this title.” 35 U.S.C.
§ 101. The Supreme Court has consistently construed
§ 101 broadly, explaining that “[i]n choosing such expan-
sive terms . . . modified by the comprehensive ‘any,’ Con-
gress plainly contemplated that the patent laws would be
given wide scope.” Bilski v. Kappos, 130 S. Ct. 3218, 3225
(2010) (quoting Chakrabarty, 447 U.S. at 308).
The Supreme Court, however, has also consistently
held that § 101, although broad, is not unlimited. Id. The
Court’s precedents provide three judicially created excep-
tions to § 101’s broad patent-eligibility principles: “laws
of nature, physical phenomena, and abstract ideas.” Id.
(quoting Chakrabarty, 447 U.S. at 309). The Court has
also referred to these exceptions as precluding the patent-
ing of phenomena of nature, mental processes, Gottschalk
v. Benson, 409 U.S. 63, 67 (1972), and products of nature,
Chakrabarty, 447 U.S. at 313 (“[T]he relevant distinction
for purposes of § 101 is . . . between products of nature . . .
and human-made inventions.”). The Court has explained
that, although not required by the statutory text, “[t]he
concepts covered by these exceptions are ‘part of the
storehouse of knowledge of all men . . . free to all men and
reserved exclusively to none.’” Bilski, 130 S. Ct. at 3225(quoting Funk Brothers Seed Co. v. Kalo Inoculant Co.,
333 U.S. 127, 130 (1948))
Plaintiffs challenge under § 101 Myriad’s composition
claims directed to “isolated” DNA molecules and method
claims directed to “analyzing” or “comparing” DNA se-
quences. We address each in turn.
37 ASSOCIATION FOR MOLECULAR v. PTO
A. Composition Claims: Isolated DNA Molecules
i.
Myriad argues that its challenged composition claims
to “isolated” DNAs cover patent-eligible compositions of
matter within the meaning of § 101. According to Myriad,
the district court came to a contrary conclusion by (1)
misreading Supreme Court precedent as excluding from
patent eligibility all “products of nature” unless “mark-
edly different” from naturally occurring ones; and (2)
incorrectly focusing not on the differences between iso-
lated and native DNAs, but on one similarity: their
informational content. Rather, Myriad argues, an iso-
lated DNA molecule is patent eligible because it is, as
claimed, “a nonnaturally occurring composition of matter”
with “a distinctive name, character, and use.” Appellant
Br. 41-42 (quoting Chakrabarty, 447 U.S. at 309-10).
According to Myriad, isolated DNA does not exist in
nature, and isolated DNAs, unlike native DNAs, can be
used as primers and probes for diagnosing cancer. More-
over, Myriad asserts that a categorical “products of na-
ture” exception not only would be unworkable, as every
composition of matter is, at some level, composed of
natural materials, but also would be contrary to this
court’s precedents, the PTO’s 2001 Utility Examination
Guidelines, and Congress’s role in enacting the patent
laws.
Plaintiffs respond that claims to isolated DNA mole-
cules fail to satisfy § 101 because such claims cover natu-
ral phenomena and products of nature. According to
Plaintiffs, Supreme Court precedent establishes that a
product of nature is not patent eligible even if, as claimed,
it has undergone some highly useful change from its
natural form. Rather, Plaintiffs assert, to be patent
eligible a composition of matter must also have a distinc-
ASSOCIATION FOR MOLECULAR v. PTO 38
tive name, character, and use, making it “markedly
different” from the natural product. In this case, Plain-
tiffs conclude that because isolated DNAs retain the same
nucleotide sequence as native DNAs, they do not have any
“markedly different” characteristics. Furthermore, ac-
cording to Plaintiffs, the isolated DNA claims also have a
preemptive effect, excluding anyone from working with
the BRCA genes.
The government as amicus curiae does not defend the
PTO’s longstanding position that isolated DNA molecules
are patent eligible, arguing instead for a middle ground.
Specifically, the government argues that DNA molecules
engineered by man, including cDNAs, 5 are patent-eligible
compositions of matter because, with rare exceptions,
they do not occur in nature, either in isolation or as
contiguous sequences within a chromosome. In contrast,
the government asserts, isolated and unmodified genomic
DNAs are not patent eligible, but rather patent-ineligible
products of nature, since their nucleotide sequences exist
because of evolution, not man.
At oral argument, the government illustrated its ar-
gument by way of a “magic microscope” test. Oral Arg. at
46:50-47:50. According to the government’s test, if an
imaginary microscope could focus in on the claimed DNA
molecule as it exists in the human body, the claim covers
unpatentable subject matter. The government thus
argues that because such a microscope could focus in on
the claimed isolated BRCA1 or BRCA2 sequences as they
exist in the human body, the claims covering those se-
quences are not patent eligible. In contrast, the govern-
5 According to the government, several of the com-
position claims at issue in this suit, including claim 2 of
the ’282 patent, are limited to cDNA and thus patent
eligible.
39 ASSOCIATION FOR MOLECULAR v. PTO
ment contends, because an imaginary microscope could
not focus in vivo on a cDNA sequence, which is engineered
by man to splice together non-contiguous coding se-
quences (i.e., exons), claims covering cDNAs are patent
eligible.
In sum, although the parties and the government ap-
pear to agree that isolated DNAs are compositions of
matter, they disagree on whether and to what degree such
molecules fall within the exception for products of nature.
As set forth below, we conclude that the challenged claims
to isolated DNAs, whether limited to cDNAs or not, are
directed to patent-eligible subject matter under § 101.
ii.
The Supreme Court’s decisions in Chakrabarty and
Funk Brothers set out the framework for deciding the
patent eligibility of isolated DNA molecules. 6
6 Other Supreme Court decisions cited by the par-
ties and amici were decided based on lack of novelty, not
patentable subject matter. In American Wood-Paper Co.
v. Fibre Disintegrating Co., the Court held the challenged
patent “void for want of novelty in the manufacture
patented,” because the “[p]aper-pulp obtained from vari-
ous vegetable substances was in common use before the
original patent was granted . . . , and whatever may be
said of their process for obtaining it, the product was in no
sense new.” 90 U.S. 566, 596 (1874). Similarly, in Coch-
rane v. Badische Anilin & Soda Fabrik, the Court held
that a claim to artificial alizarine covered an old and well-
known substance, the alizarine of madder, which could
not be patented although made artificially for the first
time. 111 U.S. 293, 311 (1884); see also id. at 308-09 (“It
is very plain that the specification of the original patent,
No. 95,465, states the invention to be a process for prepar-
ing alizarine, not as a new substance prepared for the first
time, but as the substance already known as alizarine, to
be prepared, however, by the new process, which process
ASSOCIATION FOR MOLECULAR v. PTO 40
In Chakrabarty, the Court addressed the question
whether a man-made, living microorganism is a pat-
entable manufacture or composition of matter within the
meaning of § 101. 447 U.S. at 305, 307. The microorgan-
isms were bacteria genetically engineered with four
naturally occurring DNA plasmids, each of which enabled
the breakdown of a different component of crude oil. Id.
at 305, 305 n.1. The bacteria, as a result, could break
down multiple components of crude oil, a trait possessed
by no single naturally occurring bacterium and of signifi-
cant use in more efficiently treating oil spills. Id. at 305,
305 n.2. The Court held that the bacteria qualified as
patentable subject matter because the “claim is not to a
hitherto unknown natural phenomenon, but to a non-
naturally occurring manufacture or composition of mat-
ter—a product of human ingenuity ‘having a distinctive
name, character [and] use.’” Id. at 309-10 (quoting Har-
tranft v. Wiegmann, 121 U.S. 609, 615 (1887)).
To underscore the point, the Court compared Chakra-
barty’s engineered bacteria with bacteria inoculants found
unpatentable in Funk Brothers, again casting this case
decided on obviousness in terms of § 101. See Parker v.
Flook, 437 U.S. 584, 591 (1978); Benson, 409 U.S. at 67.
In Funk Brothers, the patentee discovered that certain
strains of nitrogen-fixing bacteria associated with legu-
minous plants do not mutually inhibit each other. 333
U.S. at 129-30. Based on this discovery, the patentee
produced (and claimed) mixed cultures of nitrogen-fixing
species capable of inoculating a broader range of legumi-
nous plants than single-species cultures. Id. The Court
held that the bacteria’s qualities of non-inhibition were,
“like the heat of the sun, electricity, or the qualities of
is to be the subject of the patent, and is the process of
preparing the known product alizarine from anthracine.”
(emphases added)).
41 ASSOCIATION FOR MOLECULAR v. PTO
metals,” the “work of nature,” and thus not patentable.
Id. at 130. The Court also held that application of the
newly discovered bacterial trait of non-inhibition to create
a mixed bacterial culture was not a patentable advance
because no species acquired a different property or use.
Id. at 131. The Chakrabarty Court thus concluded that
what distinguished Chakrabarty’s bacteria from those
claimed in Funk Brothers, and made the former patent
eligible, was that Chakrabarty’s bacteria had “markedly
different characteristics from any [bacterium] found in
nature” based on the efforts of the patentee. Chakra-
barty, 447 U.S. at 310.
The distinction, therefore, between a product of na-
ture and a human-made invention for purposes of § 101
turns on a change in the claimed composition’s identity
compared with what exists in nature. Specifically, the
Supreme Court has drawn a line between compositions
that, even if combined or altered in a manner not found in
nature, have similar characteristics as in nature, and
compositions that human intervention has given “mark-
edly different,” or “distinctive,” characteristics. Id.
Hartranft, 121 U.S. at 615; see also Am. Fruit Growers v.
Brogdex Co., 283 U.S. 1, 11 (1931). Applying this test to
the isolated DNAs in this case, we conclude that the
challenged claims are drawn to patentable subject matter
because the claims cover molecules that are markedly
different—have a distinctive chemical identity and na-
ture—from molecules that exist in nature.
It is undisputed that Myriad’s claimed isolated DNAs
exist in a distinctive chemical form—as distinctive chemi-
cal molecules—from DNAs in the human body, i.e., native
DNA. Native DNA exists in the body as one of forty-six
large, contiguous DNA molecules. Each DNA molecule is
itself an integral part of a larger structural complex, a
chromosome. In each chromosome, the DNA molecule is
ASSOCIATION FOR MOLECULAR v. PTO 42
packaged around histone proteins into a structure called
chromatin, which in turn is packaged into the chromoso-
mal structure. See supra, Figure 3.
Isolated DNA, in contrast, is a free-standing portion of
a native DNA molecule, frequently a single gene. Isolated
DNA has been cleaved (i.e., had covalent bonds in its
backbone chemically severed) or synthesized to consist of
just a fraction of a naturally occurring DNA molecule.
For example, the BRCA1 gene in its native state resides
on chromosome 17, a DNA molecule of around eighty
million nucleotides. Similarly, BRCA2 in its native state
is located on chromosome 13, a DNA of approximately 114
million nucleotides. In contrast, isolated BRCA1 and
BRCA2, with introns, each consists of just 80,000 or so
nucleotides. And without introns, BRCA2 shrinks to just
10,200 or so nucleotides and BRCA1 to just around 5,500
nucleotides. Furthermore, claims 5 and 6 of the ’282
patent cover isolated DNAs having as few as fifteen
nucleotides of a BRCA sequence. Accordingly, BRCA1
and BRCA2 in their isolated state are not the same mole-
cules as DNA as it exists in the body; human intervention
in cleaving or synthesizing a portion of a native chromo-
somal DNA imparts on that isolated DNA a distinctive
chemical identity from that possessed by native DNA.
As the above description indicates, isolated DNA is
not purified DNA. Purification makes pure what was the
same material, but was previously impure. Although
isolated DNA must be removed from its native cellular
and chromosomal environment, it has also been manipu-
lated chemically so as to produce a molecule that is mark-
edly different from that which exists in the body. It has
not been purified by being isolated. Accordingly, this is
not a situation, as in Parke-Davis & Co. v. H.K. Mulford
Co., in which purification of adrenaline resulted in the
identical molecule being “for every practical purpose a
43 ASSOCIATION FOR MOLECULAR v. PTO
new thing commercially and therapeutically.” 189 F. 95,
103 (C.C.N.Y. 1911). Although, we note, Judge Learned
Hand held the claimed purified “Adrenalin” to be pat-
entable subject matter. Id. The In re Marden cases are
similarly inapposite, 7 directed as they are to the patent
ineligibility of purified natural elements—ductile ura-
nium, 47 F.2d 957 (CCPA 1931), and vanadium, 47 F.2d
958 (CCPA 1931)—that are inherently ductile in purified
form. Parke-Davis and Marden address a situation in
which claimed compound A is purified from a physical
mixture that contains compound A. In this case, the
claimed isolated DNA molecules do not exist as in nature
within a physical mixture to be purified. They have to be
chemically cleaved from their chemical combination with
other genetic materials. In other words, in nature, iso-
lated DNAs are covalently bonded to such other materi-
als. Thus, when cleaved, an isolated DNA molecule is not
7 We note that Bergy is no longer binding law.
Bergy was the companion case to Charkarbarty, and was
vacated by the Supreme Court and remanded for dis-
missal as moot. Diamond v. Chakrabarty, 444 U.S. 1028(1980). Other CCPA cases cited by the parties and amici
were not decided based on patent eligibility. In In re
Bergstrom, the court held that pure prostaglandin com-
pounds, PGE(2) and PGE(3), were improperly rejected as
lacking novelty. 427 F.2d 1394, 1394 (CCPA 1970); see
Bergy, 596 F.2d at 961 (recognizing Bergstrom as a case
decided under § 102). Similarly in In re Kratz, the court
held non-obviousness claims to synthetically produced,
substantially pure 2-methyl-2-pentenoic acid (“2M2PA”),
a chemical that gives strawberries their flavor. 592 F.2d
1169, 1170 (CCPA 1979); see also In re King, 107 F.2d
618, 619 (CCPA 1939) (holding claims to vitamin C inva-
lid for lack of novelty, as “[a]ppellants were not the first to
discover or produce [vitamin C] in its pure form”); In re
Merz, 97 F.2d 599, 601 (CCPA 1938) (holding claims to
artificial ultramarine that contains non-floatable impuri-
ties invalid as not “inventive,” and thus as obvious).
ASSOCIATION FOR MOLECULAR v. PTO 44
a purified form of a natural material, but a distinct
chemical entity. In fact, some forms of isolated DNA
require no purification at all, because DNAs can be
chemically synthesized directly as isolated molecules.
The dissent disparages the significance of a “chemical
bond,” presumably meaning a covalent bond, in distin-
guishing structurally between one molecular species and
another. But a covalent bond is the defining boundary
between one molecule and another. The dissent’s citation
of Linus Pauling’s comment that covalent bonds “make it
convenient for the chemist to consider [the aggregate] as
an independent molecular species” underlines the point.
The covalent bonds in this case separate one chemical
species from another.
Plaintiffs argue that because the claimed isolated
DNAs retain the same nucleotide sequence as native
DNAs, they do not have any “markedly different” charac-
teristics. This approach, however, looks not at whether
isolated DNAs are markedly different—have a distinctive
characteristic—from naturally occurring DNAs, as the
Supreme Court has directed, but at one similarity: the
information content contained in isolated and native
DNAs’ nucleotide sequence. Adopting this approach, the
district court disparaged the patent eligibility of isolated
DNA molecules because their genetic function is to
transmit information. We disagree, as it is the distinctive
nature of DNA molecules as isolated compositions of
matter that determines their patent eligibility rather
than their physiological use or benefit. Uses of chemical
substances may be relevant to the non-obviousness of
these substances or to method claims embodying those
uses, but the patent eligibility of an isolated DNA is not
negated because it has similar informational properties to
a different, more complex natural material that embodies
it. The claimed isolated DNA molecules are distinct from
45 ASSOCIATION FOR MOLECULAR v. PTO
their natural existence as portions of larger entities, and
their informational content is irrelevant to that fact. We
recognize that biologists may think of molecules in terms
of their uses, but genes are in fact materials having a
chemical nature and, as such, are best described in pat-
ents by their structures rather than their functions.
The district court in effect created a categorical rule
excluding isolated genes from patent eligibility. See SJ
Op., at 228-29. But the Supreme Court has “more than
once cautioned that courts ‘should not read into the
patent laws limitations and conditions which the legisla-
ture has not expressed,’” Bilski, 130 S. Ct. at 3226 (quot-
ing Diamond v. Diehr, 450 U.S. 175, 182 (1981)), and has
repeatedly rejected new categorical exclusions from
§ 101’s scope, see id. at 3227-28 (rejecting the argument
that business method patents should be categorically
excluded from § 101); Chakrabarty, 447 U.S. at 314-17(same for living organisms). We therefore reject the
district court’s unwarranted categorical exclusion of
isolated DNA molecules.
Because isolated DNAs, not just cDNAs, have a mark-
edly different chemical structure compared to native
DNAs, we reject the government’s proposed “magic micro-
scope” test, as it misunderstands the difference between
science and invention and fails to take into account the
existence of molecules as separate chemical entities. The
ability to visualize a DNA molecule through a microscope,
or by any other means, when it is bonded to other genetic
material, is worlds apart from possessing an isolated DNA
molecule that is in hand and usable. It is the difference
between knowledge of nature and reducing a portion of
nature to concrete form, the latter activity being what the
patent laws seek to encourage and protect. The govern-
ment’s microscope could focus in on a claimed portion of
any complex molecule, rendering that claimed portion
ASSOCIATION FOR MOLECULAR v. PTO 46
patent ineligible, even though that portion never exists as
a separate molecule in the body or anywhere else in
nature, and may have an entirely different utility. That
would discourage innovation. One cannot visualize a
portion of a complex molecule, including a DNA contain-
ing a particular gene, and will it into isolation as a unique
entity. Visualization does not cleave and isolate the
particular DNA; that is the act of human invention.
The parties and amici have provided many thought-
provoking hypotheticals, each of which raises a compli-
cated issue of patent eligibility not before the court.
Accordingly, we address them only briefly; courts decide
cases, they do not draft legal treatises. It is suggested
that holding isolated DNAs patent eligible opens the door
to claims covering isolated chemical elements, like lith-
ium; minerals found in the earth, like diamonds; atomic
particles, like electrons; and even organs, like a kidney,
and a leaf from a tree. None of these examples, however,
as far as we can discern, presents the case of a claim to a
composition having a distinctive chemical identity from
that of the native element, molecule, or structure. Ele-
mental lithium is the same element whether it is in the
earth or isolated; the diamond is the same lattice of
carbon molecules, just with the earth removed; the kidney
is the same kidney, the leaf the same leaf. Some may
have a changed form, quality, or use when prepared in
isolated or purified form, but we cannot tell on this record
whether the changes are sufficiently distinctive to make
the composition markedly different from the one that
exists in nature. In contrast, a portion of a native DNA
molecule—an isolated DNA—has a markedly different
chemical nature from the native DNA. It is, therefore,
patentable subject matter.
The dissent indicates that we “acknowledge[] that
elemental lithium (like other elements) would not be
47 ASSOCIATION FOR MOLECULAR v. PTO
patentable subject matter because it ‘is the same element
whether it is in earth or isolated.’” Again, these facts are
not before us, so we do not attempt to evaluate the pat-
entability of one form of lithium over another. Suffice it
to say, however, that if lithium is found in the earth as
other than elemental lithium, such as “in molecular form”
“because it reacts with air and water,” it is not the same
material as elemental lithium.
It is also important to dispute the dissent’s analogy to
snapping a leaf from a tree. With respect, no one could
contemplate that snapping a leaf from a tree would be
worthy of a patent, whereas isolating genes to provide
useful diagnostic tools and medicines is surely what the
patent laws are intended to encourage and protect.
Snapping a leaf from a tree is a physical separation, not
one creating a new chemical entity.
The dissent also mentions several times in its opinion
the breadth of certain claims as grounds for objecting to
their patentability. However, we do not have here any
rejection or invalidation on the various grounds relating
to breadth, such as in 35 U.S.C. § 112. The issue before
us is patent eligibility, not the adequacy of the patents’
disclosure to support particular claims.
Finally, our decision that isolated DNA molecules are
patent eligible comports with the longstanding practice of
the PTO. The Supreme Court has repeatedly stated that
changes to longstanding practice should come from Con-
gress, not the courts. In J.E.M. Ag Supply, Inc. v. Pioneer
Hi-Bred International, Inc., the Court rejected the argu-
ment that plants did not fall within the scope of § 101,
relying in part on the fact that “the PTO has assigned
utility patents for plants for at least 16 years and there
has been no indication from either Congress or agencies
with expertise that such coverage is inconsistent with
ASSOCIATION FOR MOLECULAR v. PTO 48
[federal law].” 534 U.S. 124, 144-45 (2001); see also Festo
Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., 535 U.S.
722, 739 (2002) (“[C]ourts must be cautious before adopt-
ing changes that disrupt the settled expectations of the
inventing community.” (citing Warner-Jenkinson Co. v.
Hilton Davis Chem. Co., 520 U.S. 17, 28 (1997))); Ariad
Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1347 (Fed.
Cir. 2010) (upholding a written description requirement
separate from enablement based in part on stare decisis).
In this case, the PTO has issued patents directed to
DNA molecules for almost thirty years. In the early
1980s, the Office granted the first human gene patents.
See Eric J. Rogers, Can You Patent Genes? Yes and No,
93 J. Pat. & Trademark Off. Soc’y 19 (2010). It is esti-
mated that the PTO has issued 2,645 patents claiming
“isolated DNA” over the past twenty-nine years, J.A.
3710, and that by 2005, had granted 40,000 DNA-related
patents covering, in non-native form, twenty percent of
the genes in the human genome, Rogers, supra at 40. In
2001, the PTO issued Utility Examination Guidelines,
which reaffirmed the agency’s position that isolated DNA
molecules are patent eligible, 66 Fed. Reg. 1092-94 (Jan.
5, 2001), and Congress has not indicated that the PTO’s
position is inconsistent with § 101. If the law is to be
changed, and DNA inventions excluded from the broad
scope of § 101 contrary to the settled expectation of the
inventing community, the decision must come not from
the courts, but from Congress.
II. Method Claims
We turn next to Myriad’s challenged method claims.
The district court’s decision predated the Supreme Court’s
decision in Bilski, which rejected this court’s machine-or-
transformation test as the exclusive test for determining
whether an invention is a patent-eligible process under
49 ASSOCIATION FOR MOLECULAR v. PTO
§ 101, although the test remains “a useful and important
clue.” 130 S. Ct. at 3227. Both parties, however, had the
opportunity to address the Court’s decision in briefing and
at oral arguments. Accordingly, we proceed to the merits,
and we conclude that all but one of Myriad’s method
claims are directed to patent-ineligible, abstract mental
processes, and fail the machine-or-transformation test.
A. Methods of “Comparing” or “Analyzing” Sequences
Myriad argues that its claims to methods of “compar-
ing” or “analyzing” BRCA sequences satisfy the machine-
or-transformation test as applied by this court in Prome-
theus because each requires a transformation—extracting
and sequencing DNA molecules from a human sample—
before the sequences can be compared or analyzed. Ac-
cording to Myriad, the district court failed to recognize the
transformative nature of the claims by (1) misconstruing
the claim term “sequence” as just information, rather
than a physical molecule; and (2) erroneously concluding,
in the alternative, that Myriad’s proposed transforma-
tions were mere data-gathering steps, rather than central
to the purpose of the claims.
Plaintiffs respond that these method claims are
drawn to the abstract idea of comparing one sequence to a
reference sequence and preempt a phenomenon of na-
ture—the correlation of genetic mutations with a predis-
position to cancer. And, according to the Plaintiffs,
limiting the claims’ application to a specific technological
field, i.e., BRCA gene sequences, is insufficient to render
the claims patent eligible. Plaintiffs also assert that the
claims do not meet the machine-or-transformation test
because the claims’ plain language includes just the one
step of “comparing” or “analyzing” two gene sequences.
We conclude that Myriad’s claims to “comparing” or
“analyzing” two gene sequences fall outside the scope of
ASSOCIATION FOR MOLECULAR v. PTO 50
§ 101 because they claim only abstract mental processes.
See Benson, 409 U.S. at 67 (“Phenomena of nature, . . .
mental processes, and abstract intellectual concepts are
not patentable, as they are the basic tools of scientific and
technological work.”). The claims recite, for example, a
“method for screening a tumor sample,” by “comparing” a
first BRCA1 sequence from a tumor sample and a second
BRCA1 sequence from a non-tumor sample, wherein a
difference in sequence indicates an alteration in the
tumor sample. ’001 patent claim 1. This claim thus
recites nothing more than the abstract mental steps
necessary to compare two different nucleotide sequences:
look at the first position in a first sequence; determine the
nucleotide sequence at that first position; look at the first
position in a second sequence; determine the nucleotide
sequence at that first position; determine if the nucleotide
at the first position in the first sequence and the first
position in the second sequence are the same or different,
wherein the latter indicates an alternation; and repeat for
the next position.
Limiting the comparison to just the BRCA genes or,
as in the case of claim 1 of the ’999 patent, to just the
identification of particular alterations, fails to render the
claimed process patent eligible. As the Supreme Court
has held, “the prohibition against patenting abstract ideas
‘cannot be circumvented by attempting to limit the use of
the formula to a particular technological environment.’”
Bilski, 130 S. Ct. at 3230 (quoting Diehr, 450 U.S. at 191-
92); see also id. at 3231 (“Flook established that limiting
an abstract idea to one field of use . . . did not make the
concept patentable.”). Although the application of a
formula or abstract idea in a process may describe pat-
entable subject matter, id. at 3230, Myriad’s claims do not
apply the step of comparing two nucleotide sequences in a
51 ASSOCIATION FOR MOLECULAR v. PTO
process. Rather, the step of comparing two DNA se-
quences is the entire process claimed.
To escape this result, Myriad attempts to read into its
method claims additional, transformative steps. As
described above, Myriad reads into its claims the steps of
(1) extracting DNA from a human sample, and (2) se-
quencing the BRCA DNA molecule, arguing that both
steps necessarily precede the step of comparing nucleotide
sequences. The claims themselves, however, do not
include either of these steps. The claims do not specify
any action prior to the step of “comparing” or “analyzing”
two sequences; the claims recite just the one step of
“comparing” or “analyzing.” Moreover, those terms’ plain
meaning does not include Myriad’s proposed sample-
processing steps; neither comparing nor analyzing means
or implies “extracting” or “sequencing” DNA or otherwise
“processing” a human sample.
Myriad claims that “comparing” and “analyzing” take
on this meaning when read in light of the patent specifi-
cations. Specifically, Myriad argues that the specifica-
tions show that the claim term “sequence” refers not to
information, but rather to a physical DNA molecule,
whose sequence must be determined before it can be
compared. We disagree. The patent specifications make
clear that “sequence” does not exclusively specify a DNA
molecule, but refers more broadly to the linear sequence
of nucleotide bases of a DNA molecule. For example,
Figure 10A-10H is described as showing the “genomic
sequence of BRCA1.” ’473 patent col.5 l.66. Figure 10
does not show a physical DNA molecule; the figure lists a
series of letters (Gs, As, Ts, and Cs) corresponding to the
nucleotides guanine, adenine, thymine, and cytosine of a
DNA molecule. Similarly, the patent specifications state
that “[t]he nucleotide sequence for BRCA1 exon 4 is
shown in SEQ ID NO: 11.” Id. col.53 ll.50-53. SEQ ID
ASSOCIATION FOR MOLECULAR v. PTO 52
NO: 11 again lists a series of Gs, As, Ts, and Cs corre-
sponding to the nucleotide sequence of BRCA1 exon 4.
Accordingly, Myriad’s challenged method claims are
distinguishable from the claims upheld under § 101 in
Prometheus. In Prometheus, the patents claimed methods
for optimizing the dosage of thiopurine drugs adminis-
tered to patients with gastrointestinal disorders. 628
F.3d at 1350. As written, the claimed methods included
the steps of (a) “administering” a thiopurine drug to a
subject, and/or (b) “determining” the drug’s metabolites
levels in the subject, wherein the measured metabolite
levels are compared with predetermined levels to optimize
drug dosage. Id. In holding that the claims satisfied
§ 101, this court concluded that, in addition to the “ad-
ministering” step being transformative, the “determining”
step was both transformative and central to the purpose
of the claims. Id. at 1357. Specifically, the court held
that because the metabolite levels could not be deter-
mined by mere inspection, the determining step necessar-
ily required a transformation: “Some form of
manipulation . . . is necessary to extract the metabolites
from a bodily sample and determine their concentration.”
Id. Moreover, we concluded that this transformation was
not just insignificant extra-solution activity or necessary
data-gathering steps, but was central to the claims,
because determining the metabolite levels was what
enabled the optimization of drug dosage. Id.
Myriad’s claims, in contrast, do not include the step of
“determining” the sequence of BRCA genes by, e.g., isolat-
ing the genes from a blood sample and sequencing them,
or any other necessarily transformative step. Rather, the
comparison between the two sequences can be accom-
plished by mere inspection alone. Accordingly, Myriad’s
claimed methods of comparing or analyzing nucleotide
sequences fail to satisfy the machine-or-transformation
53 ASSOCIATION FOR MOLECULAR v. PTO
test, and are instead directed to the abstract mental
process of comparing two nucleotide sequences. The
claims thus fail to claim a patent-eligible process under
§ 101.
B. Method of Screening Potential Cancer Therapeutics
Lastly, we turn to Myriad’s method claim directed to a
method for screening potential cancer therapeutics via
changes in cell growth rates. ’282 patent claim 20. Plain-
tiffs challenge this claim as directed to the abstract idea
of comparing the growth rates of two cell populations and
as preempting a basic scientific principle—that a slower
growth rate in the presence of a potential therapeutic
compound suggests that the compound is a cancer thera-
peutic. We disagree.
Starting with the machine-or-transformation test, we
conclude that the claim includes transformative steps, an
“important clue” that it is drawn to a patent-eligible
process. Bilski, 130 S. Ct. at 3227. Specifically, the claim
recites a method that comprises the steps of (1) “growing”
host cells transformed with an altered BRCA1 gene in the
presence or absence of a potential cancer therapeutic, (2)
“determining” the growth rate of the host cells with or
without the potential therapeutic, and (3) “comparing” the
growth rate of the host cells. The claim thus includes
more than the abstract mental step of looking at two
numbers and “comparing” two host cells’ growth rates.
The claim includes the steps of “growing” transformed
cells in the presence or absence of a potential cancer
therapeutic, an inherently transformative step involving
the manipulation of the cells and their growth medium.
The claim also includes the step of “determining” the cells’
growth rates, a step that also necessarily involves physi-
cal manipulation of the cells. Furthermore, these steps
are central to the purpose of the claimed process. See
ASSOCIATION FOR MOLECULAR v. PTO 54
Prometheus, 628 F.3d at 1356-57, 1358 (quoting In re
Bilski, 545 F.3d at 962). The goal of the claim is to assess
a compound’s potential as a cancer therapeutic, and
growing the cells and determining their growth rate is
what achieves that goal.
Furthermore, the claim is not so “manifestly abstract”
as to claim only a scientific principle, and not a patent-
eligible process. See Research Corp. Techs., Inc. v. Micro-
soft Corp., 627 F.3d 859, 869 (Fed. Cir. 2010). The claim
does not cover all cells, all compounds, or all methods of
determining the therapeutic effect of a compound.
Rather, it is tied to specific host cells transformed with
specific genes and grown in the presence or absence of a
specific type of therapeutic. Moreover, the claim is tied to
measuring a therapeutic effect on the cells solely by
changes in the cells’ growth rate. The claim thus presents
“functional and palpable applications” in the field of
biotechnology. Id. at 868; see also Prometheus, 628 F.3d
at 1355 (“[T]he claims do not preempt all uses of the
natural correlations; they utilize them in a series of
specific steps.”). Accordingly, we hold that claim 20 of the
’282 patent claims patentable subject matter under § 101.
CONCLUSION
For the foregoing reasons, we affirm the district
court’s decision to exercise declaratory judgment jurisdic-
tion over this case, we reverse the district court’s grant of
summary judgment with regard to Myriad’s composition
claims to isolated DNAs, we affirm the district court’s
grant of summary judgment with regard to Myriad’s
method claims to comparing or analyzing gene sequences,
and we reverse the district court’s grant of summary
judgment with regard to Myriad’s method claim to screen-
ing potential cancer therapeutics via changes in cell
growth rates.
55 ASSOCIATION FOR MOLECULAR v. PTO
AFFIRMED IN PART and REVERSED IN PART
No costs
United States Court of Appeals
for the Federal Circuit
__________________________
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, PHD, WENDY CHUNG, MD,
PHD, HARRY OSTRER, MD,
DAVID LEDBETTER, PHD, STEPHEN WARREN,
PHD, 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
ASSOCIATION FOR MOLECULAR v. PTO 2
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.
__________________________
2010-1406
__________________________
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.
__________________________
MOORE, Circuit Judge, concurring-in-part.
I join the majority opinion with respect to standing
and the patentability of the method claims at issue. I
believe, however, that claims directed to isolated DNA
sequences present a different set of issues. I join the
majority with respect to claims to isolated cDNA se-
quences, and concur in the judgment with respect to the
remaining sequences. I write separately to explain my
reasoning.
I.
The Patent Act, 35 U.S.C. § 101, allows “[w]hoever in-
vents or discovers any new and useful process, machine,
manufacture, or composition of matter, or any new and
useful improvement thereof” to obtain a patent. The plain
language of this statute only requires that an invention be
“new and useful,” and fall into one of four categories: a
3 ASSOCIATION FOR MOLECULAR v. PTO
“process, machine, manufacture, or composition of mat-
ter.” Congress did not impose any additional constraints
on the scope of patentable subject matter. In fact, “Con-
gress intended statutory subject matter to ‘include any-
thing under the sun that is made by man.’” Diamond v.
Chakrabarty, 447 U.S. 303, 309 (1980) (quoting the statu-
tory history).
While the plain language used by Congress did not
limit the scope of patentable subject matter in the statute,
the “Court's precedents provide three specific exceptions
to § 101's broad patent-eligibility principles: ‘laws of
nature, physical phenomena, and abstract ideas.’” Bilski
v. Kappos, 130 S. Ct. 3218, 3225 (2010) (quoting Chakra-
barty, 447 U.S. at 309). These exceptions “rest[], not on
the notion that natural phenomena are not processes [or
other articulated statutory categories], but rather on the
more fundamental understanding that they are not the
kind of ‘discoveries’ that the statute was enacted to pro-
tect.” Parker v. Flook, 437 U.S. 584, 593 (1978).
Applying the judicially created exception to the oth-
erwise broad demarcation of statutory subject matter in
section 101 can be difficult. See Funk Bros. Seed Co. v.
Kalo Inoculant Co., 333 U.S. 127, 134-45 (1948) (Frank-
furter, J., concurring) (“[T]erms as ‘the work of nature’
and the ‘laws of nature’ . . . are vague and malleable
terms . . . . Arguments drawn from such terms for ascer-
taining patentability could fairly be employed to challenge
almost every patent.”). The analysis is relatively simple if
the invention previously existed in nature exactly as
claimed. For example, naturally existing minerals, a
plant found in the wild, and physical laws such as gravity
or E=mc2 are not patentable subject matter, even if they
were “discovered” by an enterprising inventor. Chakra-
barty, 447 U.S. at 309.
ASSOCIATION FOR MOLECULAR v. PTO 4
Even though an invention did not previously exist in
nature in exactly the claimed state, however, does not
automatically mean it is patentable subject matter. For
example, in Funk Brothers, the Supreme Court held a
patent to a combination of multiple naturally occurring
bacterial strains was not patentable. Although there was
“an advantage in the combination,” which was apparently
“new and useful,” none of the bacterial strains “ac-
quire[ed] a different use” in combination. Id. at 131-32.
The aggregation of the bacterial strains into a single
product produced “no new bacteria, no change in the six
species of bacteria, and no enlargement of the range of
their utility. Each species has the same effect it always
had. The bacteria perform in their natural way. . . . They
serve the ends nature originally provided and act quite
independently of any effort of the patentee.” Id.
In contrast, the Supreme Court held bacteria that in-
cluded extra genetic material introduced by the inventor
were “a nonnaturally occurring manufacture or composi-
tion of matter—a product of human ingenuity ‘having a
distinctive name, character [and] use’” and therefore
patentable. Chakrabarty, 447 U.S. at 309-310 (quoting
Hartranft v. Wiegmann, 121 U.S. 609, 615 (1887)). Chak-
rabarty explained that there is no distinction between
inventions based on living and inanimate objects for the
purpose of the patent statute; instead, the “relevant
distinction” for the section 101 analysis is “between
products of nature . . . and human-made inventions.” Id.
at 312-13. Even if the invention was based on nature, and
resulted in a living organism, it may fall within the scope
of section 101. For example, “the work of the plant
breeder ‘in aid of nature’ was patentable invention” be-
cause “‘a plant discovery resulting from cultivation is
unique, isolated, and is not repeated by nature, nor can it
be reproduced by nature unaided by man.’” Id. (quoting
5 ASSOCIATION FOR MOLECULAR v. PTO
S. Rep. No. 315, 71st Cong., 2d Sess., 6-8 (1930)). In
Chakrabarty, the intervention of man resulted in bacteria
with “markedly different characteristics” from nature and
“the potential for significant utility,” resulting in pat-
entable subject matter. Id. at 310.
Funk Brothers and Chakrabarty do not stake out the
exact bounds of patentable subject matter. Instead, each
applies a flexible test to the specific question presented in
order to determine whether the claimed invention falls
within one of the judicial exceptions to patentability.
Funk Brothers indicates that an invention which “serve[s]
the ends nature originally provided” is likely unpat-
entable subject matter, but an invention that is an
“enlargement of the range of . . . utility” as compared to
nature may be patentable. 333 U.S. at 131. Likewise,
Chakrabarty illustrates that an invention with a distinc-
tive name, character, and use, e.g., markedly different
characteristics with the potential for significant utility, is
patentable subject matter. 447 U.S. at 309-310. Al-
though the two cases result in different outcomes, the
inquiry itself is similar.
Courts applied an analogous patentability inquiry
long before Funk Brothers or Chakrabarty. In one notable
case, Judge Learned Hand held that purified adrenaline,
a natural product, was patentable subject matter. Judge
Hand explained that even if the claimed purified adrena-
line were “merely an extracted product without change,
there is no rule that such products are not patentable.”
Parke-Davis & Co. v. H.K. Mulford Co., 189 F. 95, 103
(S.D.N.Y. 1911). This is because “while it is of course
possible logically to call this a purification of the princi-
ple” the resulting purified adrenaline was “for every
practical purpose a new thing commercially and thera-
peutically.” Id. Similarly, in a case applying the Patent
ASSOCIATION FOR MOLECULAR v. PTO 6
Act of 1952, 1 purified vitamin B-12, another natural
product, was also held patentable subject matter within
the meaning of section 101. Merck & Co. v. Olin Mathi-
eson Chem. Corp., 253 F.2d 156 (4th Cir. 1958). The
Fourth Circuit explained that purified vitamin B-12 was
“far from the premise of the [naturally occurring] princi-
ple. . . . The new product, not just the method, had such
advantageous characteristics as to replace the [naturally
occurring] liver products. What was produced was, in no
sense, an old product.” Id. at 162-63. These purified
pharmaceutical cases are both consistent with Supreme
Court precedent: the purified substance was “a new thing
. . . therapeutically,” Parke-Davis, 189 F. at 103, and had
such “advantageous characteristics” that what was pro-
duced by purification “was, in no sense, an old product.”
Merck, 253 F.2d at 162-63. In other words, the purified
natural products were held to have “markedly different
characteristics,” as compared to the impure products,
which resulted in “the potential for significant utility.”
Chakrabarty, 447 U.S. at 310.
In contrast, mere purification of a naturally occurring
element is typically insufficient to make it patentable
subject matter. For example, our predecessor court held
that claims to purified vanadium and purified uranium
were not patentable subject matter since these were
naturally occurring elements with inherent physical
properties unchanged upon purification. See In re
Marden, 47 F.2d 958, 959 (CCPA 1931) (“[P]ure vanadium
is not new in the inventive sense, and, it being a product
of nature, no one is entitled to a monopoly of the same.”);
1 The Patent Act of 1952 was the first time pat-
entable subject matter (the current section 101) was
separated out from novelty (the current section 102).
Previously, these two concepts were combined into a
single section.
7 ASSOCIATION FOR MOLECULAR v. PTO
In re Marden, 47 F.2d 957 (CCPA 1931) (“ductile ura-
nium” not patentable because uranium is inherently
ductile). Likewise, claims to purified ductile tungsten
were not patentable subject matter since pure tungsten
existed in nature and was inherently ductile. Gen. Elec.
Co. v. De Forest Radio Co., 28 F.2d 641, 643 (3d Cir.
1928). In each of these cases, purification did not result
in an element with new properties. Instead, the court
held the naturally occurring element inherently had the
same characteristics and utility (e.g. ductility) as the
claimed invention. Consistent with Funk Brothers and
Chakrabarty, the claims all fell within the laws of nature
exception.
As illustrated by these examples, courts have long ap-
plied the principles articulated in Funk Brothers and
Chakrabarty to different factual scenarios in order to
determine whether an invention, as claimed, falls into the
laws of nature exception. I see no reason to deviate from
this longstanding flexible approach in this case. Keeping
these principles in mind, I analyze the isolated DNA
claims below, to determine whether they have markedly
different characteristics with the potential for significant
utility, e.g., an “enlargement of the range of . . . utility” as
compared to nature. Chakrabarty, 447 U.S. at 309-310;
Funk Bros., 333 U.S. at 131.
II.
The majority conducts a thoughtful analysis of the
scientific principles associated with the claims at issue in
this case. I write separately here to emphasize certain
chemical considerations which I believe are particularly
important in this case.
DNA is a chemical polymer. In principle, a polymeric
DNA sequence is no different than any other well known
polymer, for example, nylon. Like any polymer, DNA is
ASSOCIATION FOR MOLECULAR v. PTO 8
made up of repeating monomer units, connected by
chemical bonds to form one larger molecule. In a DNA
sequence, the letters A, C, T, and G each represent a
different monomer unit; each monomer has a distinct
structure, with distinct properties. When they are as-
sembled into a DNA sequence, these monomers are
chemically bonded to each other. The process of polym-
erization of the monomer units—whether carried out by
chemical or biological means—results in a new molecule.
For example, the sequence A-T-C-G-T represents a single
molecule created by polymerizing five monomer units: A,
T, C, G, and T again. As illustrated by the figure below,
polymerization changes the monomers and results in a
molecule with a different ionic charge, different chemical
bonds, and a different chemical composition, as compared
to the monomers in aggregate.
9 ASSOCIATION FOR MOLECULAR v. PTO
A-T-C-G-T polymer (left) versus the A, T, C, G, T aggre-
gated monomers (right)
Deconstructing an existing DNA sequence leads to
similar results: a fragment of a DNA sequence has differ-
ent properties than the parent molecule from which it is
derived. For example, as shown below, a two nucleotide
sequence (T-C), has a different chemical structure, and
different chemical connections than the same subunit
found within the larger A-T-C-G-T structure. Despite
many similarities, it is impossible to find the isolated T-C
structure in the A-T-C-G-T molecule. This is because,
instead of being connected to a phosphate, the C subunit
terminates in a different functional group, a hydroxyl.
Likewise, instead of being connected to another sugar via
a phosphodiester bond, the T subunit instead terminates
in a phosphate. The isolated T-C sequence is a different
molecule than the “T-C” sequence appearing as part of the
ASSOCIATION FOR MOLECULAR v. PTO 10
larger A-T-C-G-T polymer. These changes are indicated
with arrows below.
A-T-C-G-T polymer (left, with T-C highlighted) versus
“isolated” T-C molecule (right)
The isolated DNA sequences at issue in this case have
the same type of chemical changes, but on a much bigger
scale. Instead of a string of five nucleotides, the chromo-
some is millions of base pairs; instead of a two-monomer
molecule, the isolated molecules claimed in this case
range from 15 nucleotides to thousands (or tens of thou-
sands) of nucleotides. Nevertheless, like the simple
sequences discussed above, just because the same series
of letters appears in both the chromosome and an isolated
DNA sequence does not mean they are the same molecule.
While the isolated DNA molecules claimed in this case are
11 ASSOCIATION FOR MOLECULAR v. PTO
undoubtedly inspired by the corresponding naturally
occurring sequence present on the chromosome, man must
create these isolated DNA molecules. This can be accom-
plished by building them de novo using chemical or bio-
logical means, or by chemically altering the larger
polymer to cleave off adjacent portions.
Isolation of a DNA sequence is more than separating
out impurities: the isolated DNA is a distinct molecule
with different physical characteristics than the naturally
occurring polymer containing the corresponding sequence
in nature. These differences, of course, are directly re-
lated to the change in chemical bonds in the isolated
DNA. Instead of being connected to many thousands of
additional nucleotides at the 3’ and 5’ ends of the se-
quence in question, as is the case in the chromosome, the
isolated DNA molecules terminate in, for example, a
hydroxyl and a phosphate group, respectively.
There are other differences between an isolated DNA
sequence and that same DNA sequence as part of the
chromosome. The DNA sequence of a gene, as it occurs in
nature, is part of a much larger structure, the chromo-
some. The claims in suit include DNA sequences as short
as fifteen nucleotides, and the isolated BRCA1 cDNA
sequence has approximately six thousand nucleotides
(see, e.g., ’282 col.67-80 (SEQ ID NO:1)). Both of these
are much smaller than the isolated full length BRCA1
gene sequence, which, as discussed below, includes both
exon and intron sequences. Even the isolated BRCA1
gene, however, is substantially smaller than chromosome
17, which includes the unisolated BRCA1 gene as well as
many other genes. J.A. 4321. Isolation of a DNA se-
quence thus results in a substantially smaller molecule
compared to the naturally occurring sequence as part of
the chromosome.
ASSOCIATION FOR MOLECULAR v. PTO 12
cDNA, unlike isolated or unisolated DNA, has a
unique sequence of DNA bases (A, C, G, T) which is not
actually present in nature. While cDNA is derived from
RNA, it has a distinctly different sequence of nucleotides,
substituting in the complementary nucleotide (swapping
G and C, and A and T/U) to form a DNA sequence that is
completely different than the corresponding RNA. There
is no contiguous sequence on the chromosome that dupli-
cates the cDNA sequence. Moreover, the naturally occur-
ring gene sequence includes both introns (which are
removed) and exons (which are included in the mature
RNA). The cDNA sequences, which are complementary to
the mature RNA, do not include the introns.
Schematic illustrating RNA splicing (J.A. 4331)
Creating isolated DNA allows a scientist, among other
things, to remove potentially confounding sequences that
are naturally present in the larger chromosomal polymer,
and instead focus on just the sequence of interest. This
aspect of isolated DNA has important practical conse-
quences and leads to additional utility, particularly for
the smaller isolated fragments. For example, a small
fragment of isolated DNA can be used as a primer in
order to selectively detect the presence of the BRCA1 gene
or BRCA1 gene mutation in a patient. Armed with this
scientific background, we can now apply the principles of
Funk Brothers and Chakrabarty to the isolated DNA
claims at issue.
13 ASSOCIATION FOR MOLECULAR v. PTO
III.
The isolated DNA claims of the patents in suit fall
into two categories. The first category of claims is di-
rected to isolated sequences that are identical to naturally
occurring gene sequences. These include claims encom-
passing both the isolated full length gene sequence (e.g.
claim 1 of ’282 patent), which are thousands of nucleo-
tides, and claims to shorter isolated DNA strands, with as
few as fifteen nucleotides, whose nucleotide sequence is
found on the chromosome (e.g. claim 5 of ’282 patent).
The second category of claims is directed to isolated DNA
sequences that are different from the naturally occurring
gene sequences. These include claims to isolated cDNA
molecules (e.g. claim 2 of the ’282 patent), which differ
from the natural gene sequence in that the introns are
removed, and are the opposite (complementary) sequence
of the naturally occurring RNA.
The cDNA claims present the easiest analysis. Al-
though the plaintiffs (now plaintiff) in the suit argue, and
the district court held, that cDNA falls within the “laws of
nature” exception to section 101 patentability, I cannot
reconcile this argument with the fact that the claimed
cDNA sequences do not exist in nature. Moreover, since
cDNA has all of the introns removed, and only contains
the coding nucleotides, it can be used to express a protein
in a cell which does not normally produce it. Of course,
the claimed isolated cDNA is inspired by nature—after
all, naturally occurring RNA is the template upon which
cDNA is constructed. Because it is used as a template,
however, cDNA has a complementary sequence of nucleo-
tides, and therefore has a completely different nucleotide
sequence than the RNA. Moreover, DNA has a different
chemical structure than RNA, including a different base
(T instead of U, respectively) and sugar units (deoxyribose
instead of ribose, respectively). This results in, among
ASSOCIATION FOR MOLECULAR v. PTO 14
other things, greater stability for the DNA sequence as
compared to the RNA sequence.
cDNA sequences thus have a distinctive name, char-
acter, and use, with markedly different chemical charac-
teristics from either the naturally occurring RNA or any
continuous DNA sequence found on the chromosome. The
claimed isolated cDNA sequences are the creation of man,
made using biological tools and the naturally occurring
mRNA as a template. cDNA is therefore not one of the
“‘manifestations of . . . nature, free to all men and re-
served exclusively to none’” that falls outside of the patent
system. Chakrabarty, 447 U.S. at 309 (quoting Funk
Bros., 333 U.S. at 130). I decline to extend the laws of
nature exception to reach entirely manmade sequences of
isolated DNA, even if those sequences are inspired by a
natural template. I therefore join the majority opinion
with respect to the claims to cDNA sequences. 2
DNA sequences that have the same pattern of DNA
bases as a natural gene, in whole or in part, present a
more difficult issue. Unlike the isolated cDNA molecules,
whose sequence is not present in nature, these kinds of
isolated DNA claims include nucleotide sequences which
are found in the human body, albeit as part of a much
larger molecule, the chromosome. The majority analysis
focuses on the “markedly different chemical structure” of
isolated DNAs, as compared to the corresponding native
DNA. Majority at 45. Although the different chemical
structure does suggest that claimed DNA is not a product
of nature, I do not think this difference alone necessarily
makes isolated DNA so “markedly different,” Chakra-
2 To the extent the claims to shorter portions of
cDNA include only naturally occurring sequences found in
the chromosome, for example claim 6 of the ’282 patent,
my reasoning is the same as for the isolated sequences of
claim 5, discussed below.
15 ASSOCIATION FOR MOLECULAR v. PTO
barty, 447 U.S. at 310, from chromosomal DNA so as to be
per se patentable subject matter. Cf. Funk Bros., 333
U.S. at 130-31 (Creation of “a new and different composi-
tion” of bacterial strains was nevertheless not patentable
subject matter).
Given the chemical differences highlighted by Judge
Lourie’s opinion and discussed supra, the mere fact that
the larger chromosomal polymer includes the same se-
quence of nucleotides as the smaller isolated DNA is not
enough to make it per se a law of nature and remove it
from the scope of patentable subject matter. The actual
molecules claimed in this case are therefore not squarely
analogous to unpatentable minerals, created by nature
without the assistance of man. Instead, the claimed
isolated DNA molecules, which are truncations (with
different ends) of the naturally occurring DNA found as
part of the chromosome in nature, are not naturally
produced without the intervention of man. Cf. Chakra-
barty, 447 U.S. at 312-13.
Given the differences, we should, as precedent in-
structs, consider whether these differences impart a new
utility which makes the molecules markedly different
from nature. I begin with the short isolated sequences
such as those covered by claim 5 which is directed to “an
isolated DNA having at least 15 nucleotides of the DNA of
claim 1.” This claim covers a sequence as short as 15
nucleotides and arguably as long as the entire gene. For
this claim to be patent eligible, all of the sequences rang-
ing from the 15 nucleotide sequence to the full gene must
be patentable subject matter. The shorter isolated DNA
sequences have a variety of applications and uses in
isolation that are new and distinct as compared to the
sequence as it occurs in nature. For example, these
sequences can be used as primers in a diagnostic screen-
ing process to detect gene mutations. These smaller
ASSOCIATION FOR MOLECULAR v. PTO 16
isolated DNA sequences—including isolated radiolabeled
sequences mirroring those on the chromosome—can also
be used as the basis for probes. Naturally occurring DNA
cannot be used to accomplish these same goals. Unlike
the isolated DNA, naturally occurring DNA simply does
not have the requisite chemical and physical properties
needed to perform these functions.
The ability to use isolated DNA molecules as the basis
for diagnostic genetic testing is clearly an “enlargement of
the range of . . . utility” as compared to nature. Funk
Bros., 333 U.S. at 131. Indeed, many of the plaintiffs in
this case submitted declarations indicating that they
wanted to either offer such testing or receive such testing.
These new applications, of course, rely on physical proper-
ties devised by nature, namely the ability of a strand of
DNA to specifically interact with a complementary
strand. Diagnostic testing, however, is not a natural
utility—the body does not naturally engage in this type of
testing, and certainly does not do so with the shorter
(non-naturally occurring) isolated DNA used by man. As
such, the claimed DNA does not “serve the ends nature
originally provided.” Id. Instead, the isolated DNA
sequences have markedly different properties which are
directly responsible for their new and significant utility.
Chakrabarty, 447 U.S. at 309-10. The same sequence, as
it appears in nature as part of the chromosome, simply
cannot be used in the same way. Because the different
chemical structure of the isolated DNA, which is a prod-
uct of the intervention of man, leads to a different and
beneficial utility, I believe small, isolated DNA fragments
are patentable subject matter.
In fact, much of the dissent’s analysis with regard to
the full gene would seem to support my conclusion that
small isolated DNA molecules are directed to patent-
eligible subject matter. The dissent explains why the
17 ASSOCIATION FOR MOLECULAR v. PTO
baseball bat is directed to patent eligible subject matter:
“man has defined the parts that are to be retained and the
parts that are to be discarded. The result of the process of
selection is a product with a function that is entirely
different from that of the raw material from which it was
obtained.” Dissent at 11. The exact same thing is true
with regard to primer and probe claims. Man has whit-
tled the chromosomal DNA molecule down to a 15 nucleo-
tide sequence—defining the parts to be retained and
discarded. And the result is a product with a function
(primer or probe) that is entirely different from the full
gene from which it was obtained. 3 I conclude that the
small, isolated DNA molecules, are an alteration of the
natural product “with markedly different characteristics
from any found in nature and one having the potential for
significant utility.” Chakrabarty, 447 U.S. at 310.
Longer strands of isolated DNA, in particular isolated
strands which include most or all of the entire gene, are a
much closer case. Some of the claims at issue, for exam-
ple ’282 patent claim 5, are genus claims, drafted broadly
enough to include both short fragments as well as the
entire isolated gene sequence. As discussed above, I
believe many species within this genus—the shorter
isolated DNA fragments—are clearly patentable subject
matter based on their new structure and corresponding
enlarged range of utility. Yet that still leaves species that
include most or all of the isolated gene sequence. While I
ultimately conclude that these longer isolated sequences,
3 The dissent analogizes the full BRCA gene to a
slab of marble found in the earth as distinct from the
sculpture carved into it, which the dissent indicates would
be worthy of intellectual property protection. If the multi-
thousand nucleotide BRCA gene is the slab, isn’t the 15
nucleotide primer the sculpture?
ASSOCIATION FOR MOLECULAR v. PTO 18
including the isolated gene sequence as a whole, are also
patentable subject matter, I do so for a reason different
than for the shorter sequences.
All of the same structural arguments apply to any
length of isolated DNA so, like the shorter strands, an
isolated DNA coding for a gene does have a literal chemi-
cal difference from the gene as it appears on the chromo-
some. Different ends in a 15 nucleotide sequence have
greater significance than different ends in a 6000 nucleo-
tide sequence. Unlike the shorter strands of isolated
DNA, the chemical and structural differences in the
isolated gene do not clearly lead to an “enlargement of the
range of . . . utility” as compared to nature. Funk Bros.,
333 U.S. at 131. For example, the full length gene is too
large to be used as a probe. See J.A. 4322 (a probe is a
DNA molecule usually 100-1,000 bases long). Likewise,
an entire isolated gene appears unsuitable for use as a
primer in genetic screening for mutations in that same
gene. See J.A. 4323 (Primers “are complementary to an
exact location of a much larger target DNA molecule.”
(emphasis added)). As such, the chemical and structural
differences in an isolated DNA sequence which includes
most or all of a gene do not clearly lead to significant new
utility as compared to nature. Whether an isolated gene
is patentable subject matter depends on how much weight
is allocated to the different structure as compared to the
similarity of the function to nature.
If I were deciding this case on a blank canvas, I might
conclude that an isolated DNA sequence that includes
most or all of a gene is not patentable subject matter.
Despite the literal chemical difference, the isolated full
length gene does not clearly have a new utility and ap-
pears to simply serve the same ends devised by nature,
namely to act as a gene encoding a protein sequence. This
case, however, comes to us with a substantial historical
19 ASSOCIATION FOR MOLECULAR v. PTO
background. Congress has, for centuries, authorized an
expansive scope of patentable subject matter. Likewise,
the United States Patent Office has allowed patents on
isolated DNA sequences for decades, and, more generally,
has allowed patents on purified natural products for
centuries. There are now thousands of patents with
claims to isolated DNA, and some unknown (but certainly
large) number of patents to purified natural products or
fragments thereof. 4 As I explain below, I believe we must
be particularly wary of expanding the judicial exception to
patentable subject matter where both settled expectations
and extensive property rights are involved. Combined
with my belief that we should defer to Congress, these
settled expectations tip the scale in favor of patentability.
5
4 See, e.g., U.S. Patent 3,067,099 (claiming vanco-
mycin, an antibiotic produced by bacteria found in soil)
and U.S. Patent 4,552,701 (claiming a vancomycin frag-
ment produced by removing a sugar unit). A natural
product fragment, for example a naturally occurring
antibiotic with a sugar moiety removed, is highly analo-
gous to isolated DNA. In each case, the claimed molecule
is a smaller fragment of a naturally occurring molecule,
with some naturally occurring functionality removed. See
U.S. Patent 4,552,701, col.3-4 (compare entry 2 with
entries 10 and 13).
5 My analysis of the claims at issue assumes that
they do not include an isolated, full length chromosome. I
do not believe that a claim to an entire chromosome, for
example chromosome 17, is patentable subject matter.
First, there is no indication that the chromosome in
isolation has markedly different characteristics compared
to the chromosome in nature. Second, unlike claims to
isolated genes, there is no indication of either settled
expectations or extensive property rights for claims to
isolated chromosomes. This is undoubtedly due to the
ASSOCIATION FOR MOLECULAR v. PTO 20
IV.
For more than a decade the Patent Office’s policy has
been that “[a]n isolated and purified DNA molecule that
has the same sequence as a naturally occurring gene is
eligible for a patent because . . . that DNA molecule does
not occur in that isolated form in nature . . . .” 66 Fed.
Reg. 1092, 1093 (Jan. 5, 2001). The explicit statement of
the Patent Office’s position on isolated DNA, however, is
simply a continuation of a longstanding and consistent
policy of allowing patents for isolated natural products.
See id. (noting U.S. Patent 141,072, claiming “[y]east, free
from organic germs of disease,” issued to Louis Pasteur in
1873); cf. In re Bergstrom, 427 F.2d 1394 (CCPA 1970)
(isolated prostaglandins patentable). According to the
Patent Office, isolated DNA is no different from the
isolated natural products of Parke-Davis. See 66 Fed.
Reg. at 1093 (quoting Parke-Davis).
Even before the current guidelines formalized the
Patent Office’s position, however, it granted patents to
human genes in the early 1980s, and subsequently issued
thousands of patents on “isolated DNA.” Majority at 48.
In fact, claims similar to the ones at issue in this case
have been the focal point of important litigation. For
example, Amgen, Inc. v. Chugai Pharmaceutical Co., 927
F.2d 1200 (Fed. Cir. 1991), involved a claim to “‘[a] puri-
fied and isolated DNA sequence consisting essentially of a
DNA sequence encoding human erythropoietin.’” Id. at
1203-04 (quoting U.S. Patent No. 4,703,008, claim 2). We
affirmed that this claim was valid and infringed. Id. at
1219. Erythropoietin, also known as EPO, went on to
become the biggest-selling biotechnology drug developed
to that point, resulted in billions of dollars in sales, and
small number of chromosomes as compared to the number
of genes.
21 ASSOCIATION FOR MOLECULAR v. PTO
accounted for over 50% of Amgen’s revenue in 1997.
Amgen, Inc. v. Hoechst Marion Roussel, Inc., 126 F. Supp.
2d 69, 77 (D. Mass. 2001). Isolated DNA claims, at least
in the case of Amgen, represent crucial and exceedingly
valuable property rights.
The settled expectations of the biotechnology indus-
try—not to mention the thousands of issued patents—
cannot be taken lightly and deserve deference. This
outpouring of scientific creativity, spurred by the patent
system, reflects a substantial investment of time and
money by the biotechnology industry to obtain property
rights related to DNA sequences. The type of fundamen-
tal alteration in the scope of patentable subject matter
argued in this case “risk[s] destroying the legitimate
expectations of inventors in their property.” Festo Corp.
v. Shoketsu Kinzoku Kogyo Kabushiki Co., 535 U.S. 722,
739 (2002). I believe leaving intact the settled expecta-
tions of property owners is particularly important in light
of the large number of property rights involved, both to
isolated DNA and to purified natural products generally.
The Supreme Court has warned that “courts must be
cautious before adopting changes that disrupt the settled
expectations of the inventing community.” Festo, 535 U.S.
at 739. The settled expectations of the inventing commu-
nity with respect to isolated DNA claims are built upon
the broad language of the statute, judicial precedent, such
as Parke-Davis and Merck, and the Patent Office’s long-
standing policy and practice. Neither Funk Brothers nor
Chakrabarty purported to overrule either the early cases
or the Patent Office’s practice; indeed, as discussed supra,
these cases weigh the same considerations as Parke-Davis
and Merck. “‘To change so substantially the rules of the
game now,’” after more than a century of practice, “‘could
very well subvert the various balances the PTO sought to
strike when issuing the numerous patents which have not
ASSOCIATION FOR MOLECULAR v. PTO 22
yet expired and which would be affected by our decision.’”
Festo, 535 U.S. at 739 (quoting Warner-Jenkinson Co. v.
Hilton Davis Chem. Co., 520 U.S. 17, 32 n.6 (1997)).
Although the Patent Office has consistently followed
the same policy for a decade (and arguably a century or
more), the United States, as an amicus represented at
argument by the Solicitor General, now argues that the
Patent Office’s published guidelines are incorrect and a
misstatement of the law. In place of these guidelines, the
Solicitor General suggested that we should use a “magic
microscope” as part of our section 101 analysis. If we
could observe the claimed substance in nature using this
microscope, the Solicitor General argues, it is not pat-
entable. The magic microscope test applies equally to
portions of a larger, naturally occurring molecule. For
example, the optical field of view could be zoomed to see
just a sequence of fifteen nucleotides within the chromo-
some. As long as you could “see” the claimed molecule in
nature using the magic microscope, it would fall into the
“laws of nature” exception and be unpatentable subject
matter.
Certainly the magic microscope has curb appeal—its
child-like simplicity an apparent virtue. The magic
microscope, however, would not see the claimed DNA
molecules at issue in this case. An isolated DNA molecule
has different chemical bonds as compared to the “uniso-
lated” sequence in the chromosome (the ends are differ-
ent). In short, the claimed molecules cannot be seen in
nature through the magic microscope. While you may be
able to see the order of DNA nucleotides in the chromo-
some, the isolated fragment of DNA is a different mole-
cule. It may be that the microscope can also break and
form chemical bonds to yield the claimed isolated DNA.
Even so, the microscope must make some decisions:
should the isolated DNA begin and end in a phosphate? a
23 ASSOCIATION FOR MOLECULAR v. PTO
hydrogen? a hydroxyl? a methyl group? an acyl group?
These decisions might be obvious to a person of ordinary
skill in the art, but they are not inherent to the unisolated
sequence as part of the chromosome. Creating the
claimed isolated DNA sequences therefore results in a
distinctly unnatural molecule. 6 Even the dissent agrees
that the isolated DNA molecules at issue require cleaving
chemical bonds, though it disputes the importance of the
resulting distinct “‘molecular species.’” Dissent at 7
(quoting Linus Pauling, The Nature of the Chemical Bond
6 (3d ed. 1960)). The magic microscope test simply does
not work the way the government claims.
While the magic microscope creates a bright line rule,
it presents a poorly defined question: can we “see” the
claimed molecule, or something fairly similar, in nature?
Even if the scientific imprecision of the test were excus-
able, the government also asks us to do away with Chak-
rabarty’s flexible inquiry as to whether the invention, as
claimed, has “markedly different characteristics from any
found in nature” which result in “the potential for signifi-
cant utility.” Id. at 310. Indeed, the bright line magic
microscope test actually appears to be contrary to Funk
Brothers, since the combination of bacteria in that case
6 This also illustrates why the government’s analo-
gies to situations dealing with elements, for example
lithium, are inapposite. Even assuming the government’s
contention that lithium does not exist in isolated form in
nature, it is nevertheless clear that elemental lithium, a
basic building block provided by nature, at some point
must have reacted with, e.g., water to form the naturally
occurring lithium salts. In contrast, an isolated DNA
sequence did not necessarily exist before reacting further
to produce the corresponding naturally occurring chromo-
somal DNA. Unlike a lithium salt, the chromosome does
not imply that an isolated DNA molecule of 15 nucleo-
tides—or even a gene—necessarily previously existed as
an isolated molecule in nature.
ASSOCIATION FOR MOLECULAR v. PTO 24
was a “new and different composition of non-inhibitive
strains,” 333 U.S. at 130-31, and therefore not actually
present in nature. There may be additional nuance in the
government’s argument that accounts for this inconsis-
tency, but under my understanding of the magic micro-
scope test, the combination in Funk Brothers would be
patentable subject matter.
Indeed, the government does not apply its own under-
standing of section 101 consistently. In its brief, the
United States explains that “[a] chemical alteration of a
bioactive molecule to improve absorption by the body . . .
would likely satisfy section 101.” United States Amicus
Br. 31 n.8. As discussed supra, the isolated DNA mole-
cules at issue in this case are the result of a “chemical
alteration of a bioactive molecule” that leads to different
properties, including a dramatic reduction in size. Just as
the government’s theoretical “chemical alteration” leads
to a molecule with improved absorption properties, the
isolation of discrete DNA sequences changes the proper-
ties of the sequence as compared to the chromosomal
DNA. This is not “[m]erely sorting the proverbial wheat
from the chaff,” id., but the creation of new DNA mole-
cules with distinct properties and additional utility,
including the ability to be used as a primer in genetic
testing. 7
7 The government’s position may be that adding
functionality to a naturally occurring molecule, for exam-
ple adding a lipid chain, is a creation of man while remov-
ing functionality, for example truncating a natural DNA
sequence or protein to yield smaller molecules with new
properties, is not. Scientifically, this distinction makes
little sense: in either case, it is the intervention of man
that created a new molecule. After all, the hand of man is
just as apparent in the David, created by removing stone
from a block of marble, as the ceiling of the Sistine
25 ASSOCIATION FOR MOLECULAR v. PTO
Also troubling is the apparent lack of awareness
about the impact of the proposed test. The government
asserts that the magic microscope “is a very limited
position”; the government is wrong. This test cannot be
limited to DNA by either legal or scientific principles. For
example, Louis Pasteur’s 1873 claim to “Yeast, free from
organic germs of disease, as an article of manufacture”
runs afoul of the magic microscope since the microscope
could zoom in to see that yeast free from contaminants.
Similarly, isolated naturally occurring molecules long
considered patentable subject matter, including adrena-
line, vitamin B-12, and prostaglandins, would also fall
outside the scope of section 101. Although the powers of
the magic microscope are not entirely clear, it appears
that patents to smaller fragments of naturally occurring
molecules, for example claims to truncated proteins (see,
e.g., U.S. Patent No. 4,762,914, entitled “Truncated Pro-
tein of Interleukin-1”), would also be unpatentable.
The government’s new test fundamentally changes
more than a century of precedent and Patent Office
practice in the pharmaceutical and biotechnology arena.
The proposed test is a purely mechanical inquiry that
fails to account for the possibility that chemical changes
to the isolated DNA sequences at issue, as compared to
their natural state, could result in markedly different
uses. As such, the government’s position in this case calls
into question the validity of an unknown number of
patents and claims and upsets the settled expectations of
some of our most innovative industries. This is not a
“very limited position.”
The dissent claims that the Patent Office’s past views
are “substantially undermined by the position the gov-
Chapel, created by adding layers of paint to an existing
structure.
ASSOCIATION FOR MOLECULAR v. PTO 26
ernment has taken in this case.” Dissent at 18. The
Patent Office’s prior practice, however, is particularly
important since it resulted in a large number of property
rights over the past decades. If the Executive decided to
change course in the Patent Office, and decline to issue
new patents to isolated genes, it would not impact these
existing property rights. This, however, is not what the
Executive argues in this case. Instead the Solicitor Gen-
eral argues for an entirely different interpretation of the
law that would destroy existing property rights. Although
the dissent points out that Chakrabarty overturned the
Patent Office’s practice of denying patents to microorgan-
isms, there is a clear difference between allowing addi-
tional patent protection where none previously existed,
and denying patent protection decades (or centuries) after
the fact, thereby eliminating a large number of property
rights. Moreover, Chakrabarty, consistent with the broad
language of the statute, allowed additional patents where
none previously existed. Here, the Solicitor General
proposes to destroy existing property rights based on a
judge made exception to that same broad language. This
is a dramatic step that I believe is best left to the legisla-
ture.
Nevertheless, the Solicitor General claims that “this is
a pure question of law” and that we can therefore feel free
to ignore the years of Patent Office practice and the
accompanying expectations that practice created within
the industry. The Solicitor General argues that we should
not defer to the broad language (all but unchanged since
1793) provided by Congress in the patent statute, or allow
Congress to decide whether it is necessary to correct the
Patent Office’s practice through legislation. It is tempting
to use our judicial power in this fashion, especially when
the patents in question raise substantial moral and
ethical issues related to awarding a property right to
27 ASSOCIATION FOR MOLECULAR v. PTO
isolated portions of human DNA—the very thing that
makes us humans, and not chimpanzees.
The Solicitor General’s invitation is tempting, but I
must decline the opportunity to act where Congress
remains silent. “[O]ur obligation is to take statutes as we
find them . . . .” Chakrabarty, 447 U.S. at 315. With
respect to section 101, “[t]he subject-matter provisions of
the patent law have been cast in broad terms to fulfill the
constitutional and statutory goal of promoting ‘the Pro-
gress of Science and the useful Arts’ . . . .” Id. Any judi-
cial exception to the statute’s broad language must be
applied with care lest the courts usurp Congress’s consti-
tutionally mandated authority to promote science and
useful arts. Judicial restraint is particularly important
here because an entire industry developed in the decades
since the Patent Office first granted patents to isolated
DNA. Disturbing the biotechnology industry’s settled
expectations now risks impeding, not promoting, innova-
tion.
Regardless, the judiciary is ill-suited to determine
whether the claims at issue promote or inhibit science and
useful arts in all but the clearest cases, for example a new
mineral discovered in the earth, or a new plant found in
the wild, or E=mc2, or the law of gravity. Instead, I leave
it to Congress, who “has the constitutional authority and
the institutional ability to accommodate fully the varied
permutations of competing interests that are inevitably
implicated by such new technology,” Sony Corp. of Amer-
ica v. Universal City Studios, Inc., 464 U.S. 417, 431
(1984), to decide whether it is necessary to change the
scope of section 101 to exclude the kind of isolated DNA
claims at issue here. “[U]ntil Congress takes such action,
this [c]ourt must construe the language of § 101 as it is.”
Chakrabarty, 447 U.S. at 318. Section 101 is, on its face,
ASSOCIATION FOR MOLECULAR v. PTO 28
broad enough to include the claims to isolated DNA at
issue here.
The dissent suggests that “this may well be one of
those instances in which ‘too much patent protection can
impede rather than ‘promote the Progress of Science and
useful Arts.’” Dissent at 17 (quoting Lab. Corp. of Am.
Holdings v. Metabolite Labs., Inc., 548 U.S. 124, 126
(2006) (Breyer, J., dissenting from dismissal of writ as
improvidently granted)). Yet the biotechnology industry
is among our most innovative, and isolated gene patents,
including the patents in suit, have existed for decades
with no evidence of ill effects on innovation. See David E.
Adelman & Kathryn L. DeAngelis, Patent Metrics: The
Mismeasure of Innovation in the Biotech Patent Debate, 85
Tex. L. Rev. 1677, 1681 (2007) (“The existing empirical
studies find few clear signs that the patenting of biotech-
nology inventions is adversely affecting biomedical inno-
vation.”); id. at 1729 (concluding “that overall
biotechnology innovation is not being impaired by the
growth in patents issued”). Changing course years after
the fact will only serve to punish those companies who
made the reasonable decision to invest large amounts of
time and money into the identification, isolation, and
characterization of genes. Unsettling the expectations of
the biotechnology industry now, based on nothing more
than unsupported supposition, strikes me as far more
likely to impede the progress of science and useful arts
than advance it. Given the complicated technology and
conflicting incentives at issue here, any change must come
from Congress. See Gottschalk v. Benson, 409 U.S. 63, 72-
73 (1972) (A section 101 analysis raises “considerable
problems . . . which only committees of Congress can
manage, for broad powers of investigation are needed,
including hearings which canvass the wide variety of
views which those operating in this field entertain. The
29 ASSOCIATION FOR MOLECULAR v. PTO
technological problems tendered [by the parties] . . .
indicate to us that considered action by the Congress is
needed.”).
In fact, Congress has at least implicitly approved of
the Patent Office’s policy of awarding patents on genes
and DNA sequences. For example, Congress included, as
part of the Patent Office’s appropriations, language
affirming the Patent Office’s interpretation of section 101
to prohibit patents on human organisms. Consolidated
Appropriations Act, 2004, Pub. L. No. 108-199, § 634, 118
Stat. 3, 101. Although Congress was aware “that there
are many institutions . . . that have extensive patents on
human genes,” 149 Cong. Rec. H7248, H7274, it explicitly
declined to implement legislation to “affect any of those
current existing patents.” Id. (statement of Mr. Weldon
introducing amendment). To the contrary, it made clear
that the language related to “human organisms” was not
intended to change the Patent Office’s policy with respect
to claims to genes, stem cells, or other similar inventions.
Id. 8 Far from oblivious to the patenting of genes, mem-
bers of Congress previously introduced bills which would
put a moratorium on gene patents, 9 authorize funding for
8 See also 149 Cong. Rec. E2417-01 (“What I want
to point out is that the U.S. Patent Office has already
issued patents on genes, stem cells, animals with human
genes, and a host of non-biologic products used by hu-
mans, but it has not issued patents on claims directed to
human organisms, including human embryos and fetuses.
My amendment would not affect the former, but would
simply affirm the latter.”) (emphasis added) (statement of
Mr. Weldon after amendment approved); see also 157
Cong. Rec. E1177-04 (resubmitting this testimony in the
context of the current patent reform legislation).
9At least one bill was introduced in Congress to put
a moratorium on patents to human genes or gene se-
ASSOCIATION FOR MOLECULAR v. PTO 30
the study of whether genes ought to be patentable, 10 and
exempt from patent infringement anyone who uses pat-
ented genes for non-commercial research purposes or
medical practitioners who use genetic diagnostic tests. 11
None of these became law. Congress is obviously aware of
the issues presented in this case and I believe “[a]ny re-
calibration of the standard of [patentability] remains in
its hands.” Microsoft Corp. v. i4i Ltd., 131 S.Ct. 2238,
2252 (2011).
This case typifies an observation by the late Chief
Judge Markey, our first Chief Judge, that “[o]nly God
works from nothing. Men must work with old elements.”
Fromson v. Advance Offset Plate, Inc., 755 F.2d 1549,
1556 n.3 (Fed. Cir. 1985) (quotation, citations omitted).
Human DNA is, for better or worse, one of the old ele-
ments bequeathed to men to use in their work. The
patents in this case revealed a new molecular understand-
ing about ourselves; “the inventions most benefiting
mankind are those that ‘push back the frontiers of chem-
istry, physics, and the like.’” Chakrabarty, 447 U.S. at
316 (quoting Great A. & P. Tea Co. v. Supermarket Corp.,
340 U.S. 147, 154 (1950)). We cannot, after decades of
quences. See, e.g., The Animal and Gene Patent Morato-
rium Bill (S.387 1993).
10 The Genomic Science and Technology Innovation
Act of 2002 (H.R. 3966).
11 The Genomic Research and Diagnostic Accessibil-
ity Act of 2002 (H.R. 3967). As the bill’s sponsor ex-
plained: “It is important to note that this section would
not overturn the commercial rights of patent holders. If a
research [organization] utilizing the exemption makes a
commercially viable finding, he or she would still have to
negotiate any rights to market the new discovery with the
patent holder.” 148 Cong. Rec. E353-03.
31 ASSOCIATION FOR MOLECULAR v. PTO
patents and judicial precedent, now call human DNA fruit
from the poisonous tree, and punish those inquisitive
enough to investigate, isolate, and patent it. “Our task
. . . is the narrow one of determining what Congress
meant by the words it used in the statute; once that is
done our powers are exhausted.” Id. at 318. This inquiry
does not have moral, ethical, or theological components.
Cf. id. at 316-17 (“[W]e are without competence to enter-
tain” arguments about “the grave risks” generated by
genetic research.). The patents in this case might well
deserve to be excluded from the patent system, but that is
a debate for Congress to resolve. I therefore decline to
extend the “laws of nature” exception to include isolated
DNA sequences.
United States Court of Appeals
for the Federal Circuit
__________________________
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, PHD, WENDY CHUNG, MD,
PHD, HARRY OSTRER, MD,
DAVID LEDBETTER, PHD, STEPHEN WARREN,
PHD, 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
ASSOCIATION FOR MOLECULAR v. PTO 2
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.
__________________________
2010-1406
__________________________
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.
__________________________
BRYSON, Circuit Judge, concurring in part and dissenting
in part:
I concur with the portions of this court’s judgment
that are directed to standing, the patentability of the
cDNA claims, and the patentability of the method claims.
I respectfully dissent, however, from the court’s holding
that Myriad’s BRCA gene claims and its claims to gene
fragments are patent-eligible. In my view, those claims
are not directed to patentable subject matter, and if
sustained the court’s decision will likely have broad
consequences, such as preempting methods for whole-
genome sequencing, even though Myriad’s contribution to
the field is not remotely consonant with such effects.
In its simplest form, the question in this case is
whether an individual can obtain patent rights to a hu-
man gene. From a common-sense point of view, most
3 ASSOCIATION FOR MOLECULAR v. PTO
observers would answer, “Of course not. Patents are for
inventions. A human gene is not an invention.” The
essence of Myriad’s argument in this case is to say that it
has not patented a human gene, but something quite
different—an isolated human gene, which differs from a
native gene because the process of extracting it results in
changes in its molecular structure (although not in its
genetic code). We are therefore required to decide
whether the process of isolating genetic material from a
human DNA molecule makes the isolated genetic mate-
rial a patentable invention. The court concludes that it
does; I conclude that it does not.
At the outset, it is important to identify the inventive
contribution underlying Myriad’s patents. Myriad was
not the first to map a BRCA gene to its chromosomal
location. That discovery was made by a team of research-
ers led by Dr. Mary-Claire King. See Jeff M. Hall et al.,
Linkage of Early-Onset Familial Breast Cancer to Chro-
mosome 17q21, 250 Science 1684 (1990). And Myriad did
not invent a new method of nucleotide sequencing. In-
stead, it applied known sequencing techniques to identify
the nucleotide order of the BRCA genes. 1 Myriad’s dis-
covery of those sequences entailed difficult work, and the
identified sequences have had important applications in
the fight against breast cancer. But the discovery of the
sequences is an unprotectable fact, just like Dr. King’s
discovery of the chromosomal location of the BRCA1 gene.
1 There is some dispute over whether other inven-
tors helped Myriad discover the BRCA sequences or
discovered the BRCA2 sequence before Myriad. Because
those disputes are irrelevant to the question of patentable
subject matter, I refer to the discovery of the BRCA
sequences as Myriad’s work.
ASSOCIATION FOR MOLECULAR v. PTO 4
Of course, Myriad is free to patent applications of its
discovery. As the first party with knowledge of the se-
quences, Myriad was in an excellent position to claim
applications of that knowledge. Many of its unchallenged
claims are limited to such applications. See, e.g., ’441
patent, claim 21; ’492 patent, claim 22; ’282 patent, claim
9. Yet some of Myriad’s challenged composition claims
effectively preempt any attempt to sequence the BRCA
genes, including whole-genome sequencing. In my view,
those claims encompass unpatentable subject matter, and
a contrary ruling is likely to have substantial adverse
effects on research and treatment in this important field.
I
As the majority and concurring opinions explain, the
claims at issue in this case fall into three categories:
claims that cover the isolated BRCA genes (claim 1 of the
’282 patent, claim 1 of the ’473 patent, and claims 1 and 6
of the ’492 patent); claims that cover only the BRCA
cDNA (claims 2 and 7 of the ’282 patent and claim 7 of the
’492 patent); and claims that cover portions of the BRCA
genes and cDNA as small as 15 nucleotides long (claims 5
and 6 of the ’282 patent). I first address the claims to the
BRCA genes.
A
In the seminal case of Diamond v. Chakrabarty, 447
U.S. 303 (1980), the Supreme Court held that an artificial
life form could be patented. In the course of its opinion,
and critically for purposes of its reasoning, the Court
stated that not all living things or other items found in
nature were subject to patenting. The Court explained
that although the language of section 101 of the Patent
Act is broad, it is not the case that it “has no limits or that
5 ASSOCIATION FOR MOLECULAR v. PTO
it embraces every discovery.” Id. at 309. The Court then
set forth the general proposition that “laws of nature,
physical phenomena, and abstract ideas have been held
not patentable.” Id. As examples, the Court noted that “a
new mineral discovered in the earth or a new plant found
in the wild is not patentable subject matter.” Thus, even
though a mineral or a plant is a “composition of matter,”
and could be viewed as falling within a broad construction
of section 101, the Court explained that those “manifesta-
tions of . . . nature” are not patentable subject matter, but
are “free to all men and reserved exclusively to none.” Id.,quoting Funk Bros. Seed Co. v. Kalo Inoculant Co., 333
U.S. 127, 130 (1948); see also Bilski v. Kappos, 130 S. Ct.
3218, 3225 (2010).
The Court in Chakrabarty held the artificial life form
at issue in that case to be patentable because the claim
was “not to a hitherto unknown natural phenomenon, but
to a nonnaturally occurring manufacture or composition
of matter—a product of human ingenuity ‘having a dis-
tinctive name, character [and] use.’” Id. at 309-10, quot-
ing Hartranft v. Wiegmann, 121 U.S. 609, 615 (1887). In
distinguishing between naturally occurring substances
and nonnaturally occurring manufactures, the Court
relied heavily on its earlier decision in Funk Brothers, in
which the inventor discovered that certain useful bacte-
rial strains did not exert an inhibitive effect on each
other. Based on that discovery, the inventor obtained a
patent on a mixed culture of those non-inhibitive strains.
The Supreme Court held the product unpatentable,
however, because the bacteria remained structurally and
functionally the same as in their natural state. Funk
Bros., 333 U.S. at 131. By contrast, because Chakrabarty
had produced “a new bacterium with markedly different
characteristics from any found in nature and one having
the potential for significant utility,” the Court held Chak-
ASSOCIATION FOR MOLECULAR v. PTO 6
rabarty’s invention to be patentable. Chakrabarty, 447
U.S. at 310.
B
Myriad’s claims to the isolated BRCA genes seem to
me to fall clearly on the “unpatentable” side of the line the
Court drew in Chakrabarty. Myriad is claiming the genes
themselves, which appear in nature on the chromosomes
of living human beings. The only material change made
to those genes from their natural state is the change that
is necessarily incidental to the extraction of the genes
from the environment in which they are found in nature.
While the process of extraction is no doubt difficult, and
may itself be patentable, the isolated genes are not mate-
rially different from the native genes. In this respect, the
genes are analogous to the “new mineral discovered in the
earth,” or the “new plant found in the wild” that the
Supreme Court referred to in Chakrabarty. It may be
very difficult to extract the newly found mineral or to
find, extract, and propagate the newly discovered plant.
But that does not make those naturally occurring items
the products of invention.
The same is true for human genes. Like some miner-
als, they are hard to extract from their natural setting.
Also like minerals, they can be used for purposes that
would be infeasible if they remained in their natural
setting. And the process of extracting minerals, or taking
cuttings from wild plants, like the process of isolating
genetic material, can result in some physical or chemical
changes to the natural substance. But such changes do
not make extracted minerals or plant cuttings patentable,
and they should not have that effect for isolated genes. In
each case, merely isolating the products of nature by
extracting them from their natural location and making
7 ASSOCIATION FOR MOLECULAR v. PTO
those alterations attendant to their extraction does not
give the extractor the right to patent the products them-
selves.
The majority characterizes the isolated genes as “new
molecules” and considers them different substances from
the corresponding native DNA. 2 Because the native
BRCA genes are chemically bonded to other genes and
histone proteins, the majority concludes that cleaving
those bonds to isolate the BRCA genes turns the isolated
genes into “different materials.” Yet there is no magic to
a chemical bond that requires us to recognize a new
product when a chemical bond is created or broken, but
not when other atomic or molecular forces are altered. 3 A
chemical bond is merely a force between two atoms or
groups of atoms strong enough “to make it convenient for
the chemist to consider [the aggregate] as an independent
molecular species.” Linus Pauling, The Nature of the
Chemical Bond 6 (3d ed. 1960). Weaker interatomic
forces will be broken when, for example, a dirty diamond
2 Although I recognize that Judge Lourie and Judge
Moore, while reaching the same ultimate conclusions,
have taken analytical paths that differ in some respects,
for convenience I will refer to Judge Lourie’s opinion as
the majority opinion and Judge Moore’s opinion as the
concurring opinion.
3 The majority characterizes the question in this
case as turning on the breaking of covalent bonds linking
the BRCA genes to the rest of the DNA in chromosomes
13 and 17, but its analysis appears to place patentable
weight on the breaking of other chemical bonds, such as
the hydrogen bonds that are broken when separating
DNA from histones or—in an example unrelated to this
case—the ionic bonds that are broken when lithium is
derived from a salt. It is difficult to see why differences
between types of chemical bonds should matter for pat-
entability purposes, and I see little support for such a
distinction in the governing precedents.
ASSOCIATION FOR MOLECULAR v. PTO 8
is cleaned with water or another solvent, but that does
not make the clean diamond a human-made invention.
See Am. Fruit Growers, Inc. v. Brogdex Co., 283 U.S. 1, 12
(1931) (cleaning a shell by acid and then grinding off a
layer with an emery wheel did not convert it into a differ-
ent product). Nor should it make a difference for pur-
poses of patentability if the portion of a wild plant that is
collected for purposes of later regeneration is separated
from the original plant by chemical means or by scissors.
Although the majority insists that the changes in the
DNA molecule that occur as part of the process of isola-
tion render the gene claims patentable, the majority does
not appear to take a similar position with respect to
chemical elements. The government as amicus curiae
argues that patenting the BRCA genes would be like
patenting the element lithium. Isolated lithium does not
occur naturally because it reacts with air and water and
thus is found in nature only as part of a chemical com-
pound, ionically bound to other elements. Robert E.
Krebs, The History and Use of Our Earth’s Chemical
Elements 48 (2d ed. 2006). Once isolated, lithium has
many industrial applications, and in order to isolate
lithium, it is necessary to break ionic bonds in the lithium
compounds that are found in nature. But the majority
acknowledges that elemental lithium (like other ele-
ments) would not be patentable subject matter because it
“is the same element whether it is in the earth or iso-
lated.”
The principles underlying that analysis apply to ge-
netic material as well. In order to isolate the BRCA gene,
it is necessary to break chemical bonds that hold the gene
in its place in the body, but the genetic coding sequence
that is the subject of each of the BRCA gene claims re-
mains the same whether the gene is in the body or iso-
9 ASSOCIATION FOR MOLECULAR v. PTO
lated. The majority, however, does not agree that the
cases are analogous, and indeed appears to have adopted
the following rule: Isolated atoms are not patent eligible,
but isolated molecules are.
Apart from the arbitrariness of such a rule, if we are
to apply the conventional nomenclature of any field to
determine whether Myriad’s isolated DNA claims are
“new,” it would seem to make more sense to look to genet-
ics, which provides the language of the claims, than to
chemistry. Aside from Myriad’s cDNA claims, its compo-
sition claims are not defined by any particular chemical
formula. For example, claim 1 of the ’282 patent covers
all isolated DNAs coding for the BRCA1 protein, with the
protein being defined by the amino acid sequence encoded
by the naturally occurring BRCA1 gene. From a molecu-
lar perspective, that claim covers a truly immense range
of substances from the cDNA that is 5,914 nucleotides
long to the isolated gene that contains more than 120,000
nucleotides. And the patent does not define the upper end
of that range because the patent does not identify a
unique nucleotide sequence for the 120,000-nucleotide-
long isolated BRCA1 gene. Instead, the patent contains a
sequence that is just 24,000 nucleotides long with numer-
ous gaps denoted “vvvvvvvvvvvvv.” ’282 patent, fig. 10.
An almost incalculably large number of new molecules
could be created by filling in those gaps with almost any
nucleotide sequence, and all of those molecules would fall
within the scope of claim 1. Included in that set are many
important molecular variations to the BRCA1 gene that
Myriad had not yet discovered and could not have chemi-
cally described. Yet those molecules would share only one
unifying characteristic: each codes for the same protein as
the naturally occurring BRCA1 gene.
ASSOCIATION FOR MOLECULAR v. PTO 10
From a genetic perspective, that claim covers one
“composition of matter”—the BRCA1 gene. The isolated
BRCA genes are identical to the BRCA genes found on
chromosomes 13 and 17. They have the same sequence,
they code for the same proteins, and they represent the
same units of heredity. During the transcription phase of
protein synthesis, the BRCA genes are separated from
chromosomal proteins. The transcription process then
proceeds from a starting point called the promoter to a
stopping point often called the terminator. James D.
Watson et al., Molecular Biology of the Gene 382, 394-96
(6th ed. 2008). The only difference between the naturally
occurring BRCA genes during transcription and the
claimed isolated DNA is that the claimed genes have been
isolated according to nature’s predefined boundaries, i.e.,
at points that preserve the ability of the gene to express
the protein for which it is coded.
In that respect, extracting a gene is akin to snapping
a leaf from a tree. Like a gene, a leaf has a natural start-
ing and stopping point. It buds during spring from the
same place that it breaks off and falls during autumn.
Yet prematurely plucking the leaf would not turn it into a
human-made invention. See Intervet Inc. v. Merial Ltd.,
617 F.3d 1282, 1295 (Fed. Cir. 2010) (Dyk, J., concurring
in part and dissenting in part). That would remain true if
there were minor differences between the plucked leaf
and the fallen autumn leaf, unless those differences
imparted “markedly different characteristics” to the
plucked leaf. Chakrabarty, 447 U.S. at 310.
Both the majority and the concurring opinions attach
significant weight to the fact that the claimed coding
portions of the native BRCA genes are part of a much
larger molecule and that the isolated BRCA genes, being
smaller molecules extracted from the larger one, are
11 ASSOCIATION FOR MOLECULAR v. PTO
therefore man-made inventions. But to argue that the
isolated BRCA gene is patentable because in its native
environment it is part of a much larger structure is no
more persuasive than arguing that although an atom may
not be patentable, a subatomic particle is patentable
because it was previously part of a larger structure, or
that while a tree is not patentable, a limb of the tree
becomes a patentable invention when it is removed from
the tree.
Of course, it is an oversimplification to say that some-
thing that can be characterized as “isolated” or “ex-
tracted” from its natural setting always remains a natural
product and is not patentable. One could say, for exam-
ple, that a baseball bat is “extracted” or “isolated” from an
ash tree, but in that case the process of “extracting” the
baseball bat necessarily changes the nature, form, and
use of the ash tree and thus results in a manmade manu-
facture, not a naturally occurring product. In that set-
ting, man has defined the parts that are to be retained
and the parts that are to be discarded. The result of the
process of selection is a product with a function that is
entirely different from that of the raw material from
which it was obtained. In the case of the BRCA genes, by
contrast, nature has defined the genes as independent
entities by virtue of their capacity for protein synthesis
and, ultimately, trait inheritance. Biochemists extract
the target genes along lines defined by nature so as to
preserve the structure and function that the gene pos-
sessed in its natural environment. In such a case, the
extraction of a product in a manner that retains the
character and function of the product as found in nature
does not result in the creation of a human invention. 4
4 By analogy, extracting a slab of marble from the
earth does not give rise to protectable intellectual prop-
ASSOCIATION FOR MOLECULAR v. PTO 12
That principle was captured by the Supreme Court’s
statement in Chakrabarty that the invention in that case
was not to “a hitherto unknown natural phenomenon, but
to a nonnaturally occurring manufacture or composition
of matter ‘having a distinctive name, character [and]
use.’” 447 U.S. at 309-10.
Cases involving the “purification” of a natural sub-
stance employ similar analysis. Our predecessor court
recognized that merely purifying a naturally occurring
substance does not render the substance patentable
unless it results in a marked change in functionality. In
re Merz, 97 F.2d 599, 601 (CCPA 1938) (holding that there
was no right to a patent on a purer version of ultrama-
rine, but recognizing that if a claimed article is “of such
purity that it differs not only in degree but in kind it may
be patentable”); see also In re King, 107 F.2d 618, 620
(CCPA 1939) (same, for purified vitamin C); In re Marden,
47 F.2d 958, 959 (CCPA 1931) (same, for purified vana-
dium); Gen. Elec. Co. v. DeForest Radio Co., 28 F.2d 641,
643 (3d Cir. 1928) (same, for purified tungsten). On the
other hand, the purified natural substance is patentable if
the “purification” results in a product with such distinct
characteristics that it becomes “for every practical pur-
pose a new thing commercially and therapeutically.”
Parke-Davis & Co. v. H.K. Mulford Co., 189 F. 95, 103
(C.C.S.D.N.Y. 1911); see also Merck & Co. v. Olin Mathi-
eson Chem. Corp., 253 F.2d 156, 161-64 (4th Cir. 1958)
(holding that a purified composition of vitamin B-12 was
patentable because the purification process resulted in a
erty rights, but “extracting” a piece of sculpture from that
slab of marble does. In the case of the BRCA gene claims,
what Myriad has claimed is more akin to the slab of
marble found in the earth than to the sculpture carved
from it after its extraction.
13 ASSOCIATION FOR MOLECULAR v. PTO
product that was therapeutically effective, whereas the
natural form was not).
In sum, the test employed by the Supreme Court in
Chakrabarty requires us to focus on two things: (1) the
similarity in structure between what is claimed and what
is found in nature and (2) the similarity in utility between
what is claimed and what is found in nature. What is
claimed in the BRCA genes is the genetic coding material,
and that material is the same, structurally and function-
ally, in both the native gene and the isolated form of the
gene.
The structural differences between the claimed “iso-
lated” genes and the corresponding portion of the native
genes are irrelevant to the claim limitations, to the func-
tioning of the genes, and to their utility in their isolated
form. The use to which the genetic material can be put,
i.e., determining its sequence in a clinical setting, is not a
new use; it is only a consequence of possession. In order
to sequence an isolated gene, each gene must function in
the same manner in the laboratory as it does in the
human body. Indeed, that identity of function in the
isolated gene is the key to its value. Moreover, as Judge
Moore’s concurring opinion explains, Myriad has failed to
credibly identify new uses for the isolated BRCA genes as
probes or primers. The naturally occurring genetic mate-
rial thus has not been altered in a way that would matter
under the standard set forth in Chakrabarty. For that
reason, the isolation of the naturally occurring genetic
material does not make the claims to the isolated BRCA
genes patent-eligible.
ASSOCIATION FOR MOLECULAR v. PTO 14
II
As noted, in addition to the BRCA gene claims dis-
cussed above, the claims at issue in this appeal include
four claims to BRCA cDNA and two claims to portions of
the BRCA genes and cDNA as small as 15 nucleotides
long.
I agree with the court that the claims to BRCA cDNA
are eligible for patenting. The cDNA cannot be isolated
from nature, but instead must be created in the labora-
tory. 5 Although that process occurs with natural machin-
ery, the end product is a human-made invention with
distinct structure because the introns that are found in
the native gene are removed from the cDNA segment.
Additionally, the cDNA has a utility not present in the
naturally occurring BRCA DNA and mRNA because
cDNA can be attached to a promoter and inserted into a
non-human cell to drive protein expression.
However, I disagree with the court as to the two
claims to short segments of DNA having at least 15
nucleotides. Claim 6 of the ’282 patent covers any se-
quence of the BRCA1 cDNA that is at least 15 nucleotides
long. That claim encompasses each BRCA1 exon, even
though each exon is naturally defined by transcription.
Moreover, because small sequences of DNA are repeated
throughout the three billion nucleotides of the human
genome, the claim covers portions of the cDNA of more
5 The appellees argue that the BRCA1 cDNA can be
isolated from nature, and they refer to a BRCA1 pseu-
dogene called BRCA1P1 that is found in the human
genome. However, the appellees have failed to demon-
strate that the pseudogene consists of the same sequence
as the BRCA1 cDNA.
15 ASSOCIATION FOR MOLECULAR v. PTO
than 4% of human genes. It also covers portions of the
DNA of nearly all human genes. Accordingly, efforts to
sequence almost any gene could infringe claim 6 even
though Myriad’s specification has contributed nothing to
human understanding of other genes.
Myriad could easily have claimed more narrowly to
achieve the utility it attaches to segments of cDNA. It
contends that those segments can be used as probes and
primers. DNA probes must be chemically altered or
“tagged” before they can be so used, and Myriad could
have claimed the tagged segments to achieve probe func-
tionality. A claim to tagged segments would not encom-
pass the BRCA1 exons. As to primer functionality, many
of the cDNA segments will not work. Some will be too
long. Some will be too short. Some will be palindromic
and fold in on themselves. Myriad could have identified a
subset of the segments that work as primers, and such a
claim could be patentable if it were limited to species with
“markedly different characteristics from any found in
nature and . . . having the potential for significant util-
ity.” Chakrabarty, 447 U.S. at 310. The problem with
claim 6 is that it is so broad that it includes products of
nature (the BRCA1 exons) and portions of other genes; its
validity is not salvaged because it includes some species
that are not natural. Accordingly, I would hold claim 6
unpatentable.
Myriad’s last claim, claim 5 of the ’282 patent, is
breathtakingly broad. That claim covers any segment of
the DNA defined by claim 1, provided that the segment is
at least 15 nucleotides long. Claim 1, in turn, covers any
isolated DNA that codes for the BRCA1 polypeptide.
Thus, claim 5 would cover not only the isolated BRCA1
gene in each of its untold molecular variations, but also
any sub-sequence of those molecules, including portions
ASSOCIATION FOR MOLECULAR v. PTO 16
that fall in the undefined range of those molecules de-
noted “vvvvvvvvvvvvv.” Claim 5 would therefore be
unpatentable for the same reasons as claim 1 and claim 6.
Of course, in light of its breadth, claim 5 of the ’282
patent is likely to be invalid on other grounds, and thus a
ruling as to patent-eligibility with respect to that claim
may be superfluous. Nonetheless, it is important to
consider the effects of such broad patent claims on the
biotechnology industry. While Myriad has emphasized
the biotechnology industry’s need of patent protection to
encourage and reward research in this difficult and
important field, there is another side to the coin. Broad
claims to genetic material present a significant obstacle to
the next generation of innovation in genetic medicine—
multiplex tests and whole-genome sequencing. New
technologies are being developed to sequence many genes
or even an entire human genome rapidly, but firms devel-
oping those technologies are encountering a thicket of
patents. Secretary’s Advisory Comm. on Genetics,
Health, and Society, Dep’t of Health & Human Servs.,
Gene Patents and Licensing Practices and Their Impact on
Patient Access to Genetic Tests 49-62 (2010). In order to
sequence an entire genome, a firm would have to license
thousands of patents from many different licensors. See
id. at 50-51. Even if many of those patents include claims
that are invalid for anticipation or obviousness, the costs
involved in determining the scope of all of those patents
could be prohibitive. See id. at 51-52; Rebecca S.
Eisenberg, Noncompliance, Nonenforcement, Nonproblem?
Rethinking the Anticommons in Biomedical Research, 45
Hou. L. Rev. 1059, 1076-1080 (2008) (concluding that
existing studies “have focused relatively little attention on
downstream product development” and that interviews
accompanying those studies suggest that, though smaller
than initially feared, the costs associated with the patent
17 ASSOCIATION FOR MOLECULAR v. PTO
thicket are “quite real in the calculations of product-
developing firms”). In light of these considerations, this
may well be one of those instances in which “too much
patent protection can impede rather than ‘promote the
Progress of Science and useful Arts.’” Lab. Corp. of Am.
Holdings v. Metabolite Labs., Inc., 548 U.S. 124, 126
(2006) (Breyer, J., dissenting from dismissal of writ as
improvidently granted).
My colleagues assign significant weight to the fact
that since 2001 the PTO has had guidelines in place that
have allowed patents on entire human genes. They
conclude that those guidelines, and the PTO’s earlier
practice, are entitled to deference from this court as to the
question whether patents to isolated human genes consti-
tute patent-eligible subject matter. I think the PTO’s
practice and guidelines are not entitled to significant
weight, for several reasons.
First, as we have recognized, the PTO lacks substan-
tive rulemaking authority as to issues such as patentabil-
ity. Animal Legal Def. Fund v. Quigg, 932 F.2d 920, 930
(Fed. Cir. 1991). In areas of patent scope, we owe defer-
ence only commensurate with the “the thoroughness of its
consideration and the validity of its reasoning.” Merck &
Co. v. Kessler, 80 F.3d 1543, 1550 (Fed. Cir. 1996). The
comments that the PTO issued at the time of its 2001
guidelines in response to suggestions that isolated human
genes were not patentable are, frankly, perfunctory. See
John M. Conley & Roberte Makowski, Back to the Future:
Rethinking the Product of Nature Doctrine as a Barrier to
Biotechnology Patents, 85 J. Pat. & Trademark Off. Soc’y
301 (2003). Because those comments, at least on their
face, do not reflect thorough consideration and study of
the issue, I do not regard them as worthy of much weight
in the analysis of this complex question.
ASSOCIATION FOR MOLECULAR v. PTO 18
Second, whatever force the PTO’s views on the issue
of patent eligibility may have had in the past has, at the
very least, been substantially undermined by the position
the government has taken in this case. The Department
of Justice filed a brief on behalf of the United States in
this court taking the position that Myriad’s gene claims
(other than the cDNA claims) are not patent-eligible.
Although the PTO did not “sign” the brief and we are left
to guess about the status of any possible continuing inter-
agency disagreements about the issue, the Department of
Justice speaks for the Executive Branch, and the PTO is
part of the Executive Branch, so it is fair to assume that
the Executive Branch has modified its position from the
one taken by the PTO in its 2001 guidelines and, infor-
mally, before that.
Finally, prior to the Supreme Court’s decision in
Chakrabarty, the PTO had determined that microorgan-
isms were not subject to patenting, but the Supreme
Court gave no indication that it regarded that view as
entitled to deference. Moreover, the Court gave short
shrift to the Commissioner’s contention (which was made
the lead argument in its brief) that the patentability of
life-forms was an issue that should be left to Congress.
Citing Marbury v. Madison, 5 U.S. (1 Cranch) 137 (1803),
the Court explained that “Congress has performed its
constitutional role in defining patentable subject matter
in § 101; we perform ours in construing the language
Congress has employed.” Chakrabarty, 477 U.S. at 315.
We have the same responsibility and should not shy away
from deciding the issues of law that the parties have
brought to us. Although my colleagues believe our analy-
sis of the legal question in this case should be influenced
by purported expectations of the inventing community
based on the PTO’s past practice of issuing patents on
human genes, that is in effect to give the PTO lawmaking
19 ASSOCIATION FOR MOLECULAR v. PTO
authority that Congress has not accorded it. 6 There is no
collective right of adverse possession to intellectual prop-
erty, and we should not create such a right. Our role is to
interpret the law that Congress has written in accordance
with the governing precedents. I would do so and would
affirm the district court’s rulings as to the BRCA gene
and BRCA gene segment claims.
6 Because the asserted reliance interest is based on
PTO practice and not on prior judicial decisions, this case
is not analogous to Warner Jenkinson Co. v. Hilton Davis
Chemical Co., 520 U.S. 17 (1997), or Festo Corp. v.
Shoketsu Kinzoku Kogyo Kabushiki Co., 535 U.S. 722(2002), where the expectations of the inventing commu-
nity were based on longstanding Supreme Court prece-
dent.