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 

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, 
ASSOCIATION FOR MOLECULAR v. PTO 2

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: August 16, 2012 

____________________________ 

CHRISTOPHER A. HANSEN, American Civil Liberties 

Union Foundation, of New York, New York, argued for 

plaintiffs-appellees. With him on 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, Public Patent Foundation, Benjamin N. Cardozo, 

School of Law, of New York, New York. 

GREGORY A. CASTANIAS, Jones Day, of Washington, 

DC, argued for all defendant-appellants. With him on the 

brief were JENNIFER L. SWIZE, of Washington, DC, ISRAEL 

SASHA MAYERGOYZ and DENNIS MURASHKO, of Chicago, 

Illinois, BRIAN M. POISSANT, LAURA A. CORUZZI and 

EILEEN FALVEY, of New York, New York. Of counsel were 

BENJAMIN JACKSON, and JAY Z. ZHANG, Myriad Genetics, 

of Salt Lake City, Utah. 

MELISSA N. PATTERSON, Attorney, Civil Division, Appellate Staff, United States Department of Justice, of 
3 ASSOCIATION FOR MOLECULAR v. PTO

Washington, DC, argued for amicus curiae, United States. 

With her on the brief were STUART F. DELERY, Acting 

Assistant Attorney General, BETH S. BRINKMANN, Deputy 

Assistant Attorney General and SCOTT R. MCINTOSH, 

Attorney. Of counsel was MARK R. FREEMAN. 

THOMAS J. KOWALSKI, Vedder Price PC, of New York, 

New York, for amicus curiae Protein Sciences Corporation. With him on the brief were DEBORAH L. LU; and 

ROBERT S. RIGG, of Chicago, Illinois. 

ROBERT A. ARMITAGE, Eli Lilly and Company, Indianapolis, Indiana, for amicus curiae, Eli Lilly and Company. 

With him on the brief was JAMES J. KELLEY. 

CHRISTOPHER M. HOLMAN, University of MissouriKansas City School of Law, of Kansas City, Missouri, for 

amicus curiae Law Professor Christopher M. Holman. 

CHARLES R. MACEDO, Amster Rothstein & Ebenstein, 

LLP, of New York, New York, for amicus curiae, New 

York Intellectual Property Law Association. Of counsel 

on the brief were RONALD M. DAIGNAULT and MATTHEW B.

MCFARLANE, Robins, Kaplan, Miller & Ciresi, L.L.P. of 

New York, New York. 

LORI B. ANDREWS, IIT Chicago-Kent College of Law, of 

Chicago, Illinois, for amicus curiae, The American College 

of Embryology, et al. Of counsel was JOSHUA D. SARNOFF, 

DePaul University College of Law, of Chicago, Illinois. 

DEBRA L. GREENFIELD, UCLA Institute for Society and 

Genetics, of Los Angeles, California, for amici curiae, The 

National Women’s Health Network, et al. 
ASSOCIATION FOR MOLECULAR v. PTO 4

KRISTA L. COX, Knowledge Ecology International, of 

Washington, DC, for amicus curiae, Knowledge Ecology 

International, et al. 

RICHARD F. PHILLIPS, Intellectual Property Owners 

Association, of Washington, DC, for amicus curiae, Intellectual Property Owners Association. With him on the 

brief was KEVIN H. RHODES. Of counsel on the brief were 

PAUL H. BERGHOFF, KEVIN E. NOONAN and JEFFREY P.

ARMSTRONG, McDonnell Boehnen Hulbert & Berghoff, 

LLP, of Chicago, Illinois. Of counsel were HERBERT C.

WAMSLEY, Intellectual Property Owners, of Washington, 

DC, and DOUGLAS KENT NORMAN, Eli Lilly & Company, of 

Indianapolis, Indiana. 

BARBARA R. RUDOLPH, Finnegan, Henderson, 

Farabow, Garrett & Dunner, LLP, of Washington, DC, for 

amicus curiae, American Intellectual Property Law Association. With her on the brief were ROBERT D. LITOWITZ, 

ERIKA HARMON ARNER and DAVID S. FORMAN. Of counsel 

on the brief was WILLIAM G. BARBER, American Intellectual Property Law Association, of Arlington, Virginia. Of 

counsel were DAVID WARREN HILL, American Intellectual 

Property, of Arlington, Virginia, and ROBERT C. STANLEY, 

Finnegan, Henderson, Farabow, Garrett & Dunner, LLP, 

of Atlanta, Georgia. 

WILLIAM T. ROBINSON, III, American Bar Association, 

of Chicago, Illinois, for amicus curiae, American Bar 

Association. Of counsel on the brief were JOHN P.

ELWOOD, Vinson & Elkins, LLP, of Washington, DC; and 

MICHAEL A. VALEK, STEPHEN C. STOUT, of Austin, Texas. 

MARK J. GATSCHET, Mark John Gatschet, P.L.L.C., of 

Houston, Texas, for amicus curiae, Mark J. Gatschet and 
5 ASSOCIATION FOR MOLECULAR v. PTO

Richard W. Knight. Of counsel on the brief was RICHARD 

W. KNIGHT, R.W. Knight P.C. of San Antonio, Texas. 

CLAIRE LAPORTE, Foley Hoag, LLP, of Boston, Massachusetts, for amicus curiae Federal Circuit Bar Association. With her on the brief was JAMES M. FLAHERTY, JR. 

JOHN L. HENDRICKS, Hitchcock Evert, LLP, of Dallas, 

Texas, for amicus curiae, AARP, et al. With him on the 

brief were MEGAN M. O’LAUGHLIN and JOHN T. TOWER. Of 

counsel was MICHAEL R. SCHUSTER. 

J. TIMOTHY KEANE, Harness, Dickey & Pierce, PLC, of 

St. Louis, Missouri, for amicus curiae, BioGenerator, et al 

SUSAN E. MCBEE, Baker, Donelson, Bearman, Caldwell, and Berkowitz, P.C., of Washington, DC, for amicus 

curiae, Immatics Biotechnologie, GmbH. With her on the 

brief was BRYAN W. JONES. 

SETH P. WAXMAN, Wilmer Cutler Pickering Hale and 

Dorr, LLP, of Washington, DC, for amicus curiae, Biotechnology Industry Organization, et al. With him on the 

brief was THOMAS G. SAUNDERS. Of counsel on the brief 

was MARK C. FLEMING, of Boston, Massachusetts, and 

HANSJORG SAUER, Biotechnology Industry Organization, 

of Washington, DC. Of counsel was ALLEN C. NUNNALLY, 

Wilmer Cutler Pickering Hale and Dorr, LLP, of Boston, 

Massachusetts. 

Jennifer Gordon, Baker Botts, L.L.P. of New York, 

New York, for amicus curiae, Croplife International. 

With her on the brief were STEVEN LENDARIS and 

JENNIFER C. TEMPESTA. 
ASSOCIATION FOR MOLECULAR v. PTO 6

MATTHEW J. DOWD, Wiley Rein LLP, of Washington, 

DC, for amicus curiae, JAMES D. WATSON. With him on 

the brief was JAMES H. WALLACE, JR. 

KURT G. CALIA, Covington & Burling, LLP, of Redwood Shores, California, for amicus curiae, Pharmaceutical Research and Manufacturers of America. With him on 

the brief were ROBERT A. LONG, JR. and ALLISON E.

KERNDT, of Washington, DC, and ALEXA R. HANSEN, of 

San Francisco, California. 

EILEEN M. KANE, Penn State Dickinson School of Law, 

of University Park, Pennsylvania, for amicus curiae, 

Professor Eileen M. Kane. 

GENEVIEVE E. SCOTT, Yale School of Law, of Brooklyn, 

New York, for amicus curiae, Information Society Project 

at Yale Law School Scholars. With her on the brief was 

PRISCILLA J. SMITH. 

ROBERT SACHS, Fenwick & West, LLP, of San Francisco, California, for amicus curiae, Advanced Biological 

Laboratories, SA. 

__________________________ 

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 University of Utah Research Foundation (collectively, “Myriad”) 

appeal from the decision of the United States District 
7 ASSOCIATION FOR MOLECULAR v. PTO

Court for the Southern District of New York holding that 

an assortment of medical organizations, researchers, 

genetic counselors, and patients (collectively, “Plaintiffs”) 

have standing under the Declaratory Judgment Act to 

challenge Myriad’s patents. Ass’n for Molecular Pathology 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 nonpatentable subject matter under 35 U.S.C. § 101. Ass’n 

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. 

This appeal has returned to us as, a petition for certiorari having been filed from our decision of July 29, 

2011, the Supreme Court of the United States granted the 

petition, vacated our decision, and remanded the case to 

us for further consideration in light of its decision in Mayo 

Collaborative Services v. Prometheus, Inc., 566 U.S. ___, 

132 S. Ct. 1289 (2012). Ass’n for Molecular Pathology v. 

Myriad Genetics, Inc., 132 S. Ct. 1794 (2012). We invited 

and received briefing by the parties and interested amici 

and held oral argument on July 20, 2012. Our decision on 

remand follows. It both decides the issues that were 

before us in the original appeal and evaluates the effect of 

Mayo on those issues. 

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 plaintiff, 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 because each of the 

claimed molecules represents a nonnaturally occurring 
ASSOCIATION FOR MOLECULAR v. PTO 8

composition of matter. We also reverse the district court’s 

decision that Myriad’s method claim to screening potential cancer therapeutics via changes in cell growth rates of 

transformed cells is directed to a patent-ineligible scientific principle. We affirm the court’s decision, however, 

that Myriad’s method claims directed to “comparing” or 

“analyzing” 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., 669 F. 

Supp. 2d at 369-76. Specifically, Plaintiffs sought a 

declaration that fifteen claims from seven patents assigned to Myriad are drawn 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 “isolated” human genes, BRCA1 and BRCA2 (collectively, 

“BRCA1/2” or “BRCA”), and certain alterations, or mutations, 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 polypeptide, said polypeptide having the amino acid sequence set forth in SEQ ID NO:2. 
9 ASSOCIATION FOR MOLECULAR v. PTO

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. 

’282 patent col.153 l.55 – col.154 l.56.1 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; the latter sequence is colloquially referred to as cDNA. Id. 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 claims 1 of the ’999 

and ’001 patents: 

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 Tables 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 sequence of BRCA1 cDNA made from mRNA from 

said human sample with the proviso that said 

germline alteration is not a deletion of 4 nucleotides corresponding to base numbers 4184-4187 of 

SEQ ID NO:1. 

’999 patent col.161 ll.17-25 (emphases added). 

 1 In addition to representative claims 1, 2, and 5 of 

the ’282 patent, other claims to isolated DNA molecules at 

issue in this appeal include: claims 6 and 7 of the ’282 

patent; claims 1, 6, and 7 of the ’492 patent; and claim 1 

of the ’473 patent. 
ASSOCIATION FOR MOLECULAR v. PTO 10

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 tumor 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 alteration in the BRCA1 gene in said tumor sample. 

’001 patent col.155 ll.2-17 (emphasis added).2 

The final method claim challenged by Plaintiffs is directed to a method of screening potential cancer therapeutics. Specifically, claim 20 of the ’282 patent reads as 

follows: 

20. A method for screening potential cancer 

therapeutics which comprises: growing a transformed eukaryotic host cell containing an altered 

BRCA1 gene causing cancer in the presence of a 

compound suspected of being a cancer therapeutic, growing said transformed eukaryotic host cell

in the absence of said compound, determining the 

 2 The claims currently before us that recite methods 

of “analyzing” or “comparing” BRCA sequences are: claims 

1 of the ’999, ’001, and ’441 patents and claims 1 and 2 of 

the ’857 patent. 
11 ASSOCIATION FOR MOLECULAR v. PTO

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 comparing the growth rate of said host cells, wherein a 

slower rate of growth of said host cell in the presence of said compound is indicative of a cancer 

therapeutic. 

’282 patent col.156 ll.13–24 (emphases added). 

The challenged claims thus relate to isolated gene sequences 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 beings.3 The human genome, the entirety of human genetic 

information, contains approximately 22,000 genes, which 

form the basis of human inheritance. The majority of 

genes act by guiding the production of polypeptide chains 

that form proteins. Proteins in turn make up living 

matter and catalyze a variety of cellular processes. 

Chemically, the human genome is composed of deoxyribonucleic 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,4 together via a sugar-

 3 The district court’s opinion, SJ Op., 702 F. Supp. 

2d at 192-203, contains a detailed and comprehensive 

discussion of the science involved in this case. We repeat 

only the basics here. 

4 Covalent bonds are chemical bonds characterized 

by the sharing of electrons between atoms in a molecule. 
ASSOCIATION FOR MOLECULAR v. PTO 12

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 molecule 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 nucleotides 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 

gene, e.g., the BRCA1 gene encodes for the BRCA1 protein. Most genes have both “exon” and “intron” sequences. 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 
13 ASSOCIATION FOR MOLECULAR v. PTO

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”). During transcription, the DNA double 

helix is unwound and each nucleotide on the non-coding, 

or template, DNA strand is used to make a complementary, single-stranded RNA molecule that mirrors the 

coding DNA strand, i.e., adenine on the template DNA 

strand results in uracil in the RNA molecule, 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, followed by “splicing” the exons 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 excising the introns and

splicing of the exons to produce an mRNA containing only 

exon sequences. 

Figure 2 
ASSOCIATION FOR MOLECULAR v. PTO 14

Following transcription and splicing, the resulting 

mRNA is “translated” into the encoded protein. Genes, 

and their corresponding mRNAs, encode proteins via 

three-nucleotide combinations called codons. Each codon 

triplet corresponds to one of the twenty amino acids that 

make up all proteins or a “stop” signal that terminates 

protein translation. For example, the codon adeninethymine-guanine (ATG, or AUG in the corresponding 

mRNA), encodes the amino acid methionine. The relationship between the sixty-four possible codon sequences 

and their corresponding 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. 

Figure 3 

Changes, or mutations, in the sequence of a human 

gene can alter the production, structure, and/or function 

of the resulting protein. Small-scale changes include 

point mutations in which a change to a single nucleotide 
15 ASSOCIATION FOR MOLECULAR v. PTO

alters a single amino acid in the encoded protein. For 

example, a base change in the codon GCU to CCU 

changes an alanine in the encoded protein to a proline. 

Larger scale variations include the deletion, rearrangement, or duplication of larger DNA segments—ranging 

from several hundreds to over a million nucleotides—and 

can 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 determine whether a gene contains 

mutations associated with a particular disease or disease 

risk. 

Nearly every cell in the human body contains an individual’s entire genome. DNA in the cell, called “native” or 

“genomic” DNA, is packaged into twenty-three pairs of 

chromosomes. Chromosomes are complex structures 

comprising a single extended DNA molecule wrapped 

around proteins called histones, as shown in Figure 4 

below. 
ASSOCIATION FOR MOLECULAR v. PTO 16

Figure 4 

Each chromosome contiguously spans millions of bases 

and encompasses many discrete genes. Humans have 

twenty-two pairs of autosomal chromosomes, 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 chromosome in males. 

Genomic DNA can be extracted from its cellular environment 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 complementary base pairing in a manner analogous to RNA 
17 ASSOCIATION FOR MOLECULAR v. PTO

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 

chromosomal gene sequence. 

II. 

Certain mutations in the BRCA genes correlate with 

an increased 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 hereditary breast and ovarian cancers, and thus aids in the 

difficult decision regarding whether to undertake preventive options, including prophylactic surgery. Diagnostic 

results can also be an important factor in structuring an 

appropriate course of cancer treatment, since certain 

forms of therapy are more effective in treating cancers 

related to BRCA mutations. 

The inventors of the patents in suit identified the genetic 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 occurrence of cancer in individual family members with the 

inheritance of certain marker DNA sequences. This 

allowed the inventors to identify, or “map,” the physical 
ASSOCIATION FOR MOLECULAR v. PTO 18

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.5 

III. 

Myriad, however, was not the only entity to implement 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, however, accusations by Myriad that GDL’s BRCA testing 

services infringed its patents forced the lab to stop providing such services. 

The first sign of a dispute came in early 1998. At that 

time, Dr. Kazazian recalls a dinner with Dr. Mark Skolnick, inventor and Chief Science Officer 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 Myriad. The letter stated that Myriad knew that Kazazian 

was currently providing BRCA1 diagnostic testing services, and that Myriad, as patent holder of five U.S. 

patents covering the isolated BRCA1 gene and diagnostic 

 5 Myriad filed the first patent application leading to 

the patents in suit covering isolated BRCA1 DNA and 

associated diagnostic methods in August 1994. The first 

resulting 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 

such patent, the ’492 patent, issued on November 17, 

1998. 
19 ASSOCIATION FOR MOLECULAR v. PTO

testing, was making available to select institutions a 

collaborative license. Attached to the letter was a copy of 

Myriad’s collaborative agreement, which proposed severely 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 laboratory 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 alterations in the BRCA1 sequence.” J.A. 1145. 

The letter also indicated that it “has come to Myriad’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 

the University of Pennsylvania, received a similar ceaseand-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 

Pennsylvania is continuing to willfully engage in commercial BRCA1 and BRCA2 genetic testing activities, in 
ASSOCIATION FOR MOLECULAR v. PTO 20

violation of the University of Pennsylvania’s previous 

assurances that such commercial testing activities would 

be discontinued.” 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 

accepting 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, 

which became (and remains today) the only provider of 

such services in the United States. 

During this period, Myriad also initiated several patent 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 vigorous 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

testing, either covered by their insurance or at a price 
21 ASSOCIATION FOR MOLECULAR v. PTO

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. Dr. Ostrer6 also indicates that 

his lab has all the personnel, facilities, and expertise 

necessary 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 standing to bring a declaratory judgment suit challenging the 

validity of its patents. The district court disagreed, 

 6 On July 27, 2011, two days before we issued our 

initial, now-vacated decision in this case, Myriad notified 

the court that Dr. Ostrer was leaving NYU to assume a 

position at the Albert Einstein College of Medicine and 

Montefiore Medical Center, effective August 29, 2011. In 

response, Plaintiffs submitted a supplemental declaration 

from Dr. Ostrer stating that, in his new position, he still 

seeks to undertake BRCA diagnostic testing, still has the 

resources and expertise to conduct such testing, and 

would immediately do so if Myriad’s patents were invalidated. Following remand from the Supreme Court, we 

have also received from Myriad a related “suggestion of 

mootness” and motion to remand or dismiss. We declined 

the suggestion and denied the motion. We now review 

this case on the facts and arguments briefed and presented to us. 
ASSOCIATION FOR MOLECULAR v. PTO 22

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., 669 F. 

Supp. 2d 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 

communications, cease-and-desist letters, licensing offers, 

and litigation,” 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 concluded, had placed “the Plaintiffs in precisely the situation 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 Plaintiffs, 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 alleged sufficient meaningful preparations for infringement 

to establish declaratory judgment jurisdiction. Id. at 390-
23 ASSOCIATION FOR MOLECULAR v. PTO

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. 

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 nonpatentable subject matter and thus invalid under § 101. 

SJ Op., 702 F. Supp. 2d 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 machine-or-transformation test. Id. at 233 (citing In re 

Bilski, 545 F.3d 943 (Fed. Cir. 2008) (en banc), aff’d on 

other grounds, 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 
ASSOCIATION FOR MOLECULAR v. PTO 24

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 

Mayo based on the “determining” step in the latter being 

construed to include the extraction and measurement of 

metabolite levels from a patient sample. SJ Op., 702 F. 

Supp. 2d at 234-35 (citing Prometheus Labs., Inc. v. Mayo 

Collaborative Servs., 628 F.3d 1347, 1350 (Fed. Cir. 2010), 

rev’d, 132 S. Ct. 1289 (2012)). 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 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 interested 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-
25 ASSOCIATION FOR MOLECULAR v. PTO

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.” MedImmune, 549 U.S. at 127 (quoting Aetna Life, 300 U.S. at 

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 judgment.” Id. (quoting Md. Cas. Co. v. Pac. 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 controversy: 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, 
ASSOCIATION FOR MOLECULAR v. PTO 26

504 U.S. 555, 560 (1992). “First, the plaintiff must have 

suffered an injury in fact—an invasion of a legally protected interest which is (a) concrete and particularized, 

and (b) actual or imminent, not conjectural or hypothetical.” 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). 

“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 governed by Federal Circuit law.” MedImmune, Inc. v. Centocor, 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 establish an injury in fact traceable to the patentee, a declaratory 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 judgment jurisdiction in light of 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 
27 ASSOCIATION FOR MOLECULAR v. PTO

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. Kazazian, 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. 

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 continues to suppress their ability to perform clinical BRCA

testing, placing Plaintiffs in the very dilemma the Declaratory 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-
ASSOCIATION FOR MOLECULAR v. PTO 28

dertake the BRCA-related activities that they desire 

because of Myriad’s enforcement of its patent rights 

covering BRCA1/2.7 Only three plaintiffs, however, 

allege an injury traceable to Myriad; only Drs. Kazazian, 

Ganguly, and Ostrer allege affirmative patent enforcement 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 restrictive “reasonable apprehension of suit” test for declaratory 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 defendants,” Prasco, LLC v. Medicis Pharm. Corp., 537 F.3d 

1329, 1339 (Fed. Cir. 2008). Accordingly, following 

MedImmune, this court has continued to hold that declaratory judgment jurisdiction will not arise merely on 

the basis that a party learns of the existence of an adversely 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 

 7 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. 
29 ASSOCIATION FOR MOLECULAR v. PTO

“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 BRCArelated 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 making available to his institution, NYU Medical Center, a 

limited collaborative license. The collaborative license 

required NYU to make a payment to Myriad for each nonresearch 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 circumstances. 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 infringement suit by Myriad against the University of Pennsyl-
ASSOCIATION FOR MOLECULAR v. PTO 30

vania, which was later dismissed without prejudice after 

the University agreed to cease all accused BRCA testing 

services. Myriad also sued Oncormed for patent infringement 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 patentineligible products of nature. Acting on his belief, Ostrer 

seeks in this lawsuit a declaration of his right to undertake BRCA-related clinical activities without a license. 

Accordingly, Myriad and Dr. Ostrer have taken adverse 

legal positions regarding whether or not Ostrer can engage 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 declaratory 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 BRCArelated 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 hypothetical state of facts,” Aetna Life, 300 U.S. at 241, but rather 
31 ASSOCIATION FOR MOLECULAR v. PTO

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 immediately undertake clinical BRCA testing, but also states 

unequivocally that he will immediately begin such testing. 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” resuming BRCA testing. These “‘some day’ intentions” are 

insufficient to support an “actual or imminent” injury for 

standing “without . . . any specification of when the some 

day will be.” Lujan, 504 U.S. at 564. As a result, Drs. 

Kazazian and Ganguly do not have standing. 

Myriad seeks to avoid 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., Appellants’ Br., 2010 WL 4600106, at 26 

(“[A] patentee’s ten-year silence presumptively extinguishes any reasonable objective fear of suit.”). We disagree. In many cases a controversy 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.8 

 8 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

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 challenged 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 

isolated BRCA genes and the diagnostic step of comparing 

the genes’ sequences. 

Second, ever since Myriad’s enforcement efforts eliminated all competition, Myriad and Ostrer have not altered 

their respective positions. Ostrer, still laboring under 

Myriad’s threat of infringement liability, has not attempted 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, consistent 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. 
33 ASSOCIATION FOR MOLECULAR v. PTO

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 without 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 determining 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. 
ASSOCIATION FOR MOLECULAR v. PTO 34

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 declaratoryjudgment action to obtain piecemeal adjudication of 

defenses that would not finally and conclusively resolve

the underlying controversy.”). Specifically, Myriad asserts 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 sequencing, a favorable decision will not redress the Plaintiffs’ 

alleged injury. Again, we disagree. 

The Supreme Court has required only that it is 

“likely,” rather than “merely ‘speculative,’” that the alleged 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 Metropolitan Housing Development Corp. (“MHDC”) had contracted 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 sufficient that there was a “substantial probability” that the 

housing development would be built. Id. at 261, 264. 
35 ASSOCIATION FOR MOLECULAR v. PTO

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’ invalidity would remove that barrier. See id. at 261. Moreover, 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 Plaintiffs’ counsel stated at the first oral argument in this case 

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 construe the asserted claims and decline to hold 

on this record that Dr. Ostrer’s proposed BRCA-related 

activities would infringe unchallenged 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. 

Although we affirm the district court’s decision to exercise declaratory judgment jurisdiction over this case, we 

do so on narrower grounds. The district court failed to 

limit its jurisdictional holding to affirmative acts by the 

patentee directed at specific Plaintiffs, see SanDisk, 480 

F.3d at 1380-81, erroneously holding all the Plaintiffs had 

standing based on “the widespread understanding that 

one may engage in BRCA1/2 testing at the risk of being 

sued for infringement liability by Myriad,” DJ Op., 669 F. 

Supp. 2d 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 declaratory judgment action. Simply disagreeing with the existence of a patent on isolated DNA sequences or even 
ASSOCIATION FOR MOLECULAR v. PTO 36

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. 

The various organizational plaintiffs in this suit in particular were not the target of any enforcement action or 

offered license agreements by Myriad and had made no 

preparation to undertake potentially infringing activities. 

They accordingly suffered no injury and thus lack standing to bring this action. See Prasco, 537 F.3d at 1338-42; 

Cat Tech, 528 F.3d at 880-81. 

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. Subject Matter Eligibility 

Under the Patent Act, “Whoever invents or discovers 

any new and useful process, machine, manufacture, or 

composition of matter, or any new and useful improvement thereof, may obtain a patent 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 expansive terms . . . modified by the comprehensive ‘any,’ Congress 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 exceptions to § 101’s broad patent-eligibility principles: “‘Laws 
37 ASSOCIATION FOR MOLECULAR v. PTO

of nature, natural phenomena, and abstract ideas’ are not 

patentable.” Mayo, 132 S. Ct. at 1293 (quoting Diamond 

v. Diehr, 450 U.S. 175, 185 (1981)). The Court has also 

referred to those exceptions as precluding the patenting of 

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 Bros. 

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, its method 

claims directed to “analyzing” or “comparing” DNA sequences, and its claim to a method for screening potential 

cancer therapeutics. We address each in turn. Before 

reviewing the applicability of the Supreme Court’s Mayo

holding to the claims of the Myriad patents, however, it is 

important to state what this appeal is not about. It is not 

about whether individuals suspected of having an increased risk of developing breast cancer are entitled to a 

second opinion. Nor is it about whether the University of 

Utah, the owner of the instant patents, or Myriad, the 

exclusive licensee, has acted improperly in its licensing or 

enforcement policies with respect to the patents. The 

question is also not whether is it desirable for one company to hold a patent or license covering a test that may 

save people’s lives, or for other companies to be excluded 

from the market encompassed by such a patent—that is 

the basic right provided by a patent, i.e., to exclude others 

from practicing the patented subject matter. It is also not 

whether the claims at issue are novel or nonobvious or too 
ASSOCIATION FOR MOLECULAR v. PTO 38

broad. Those questions are not before us. It is solely 

whether the claims to isolated BRCA DNA, to methods for 

comparing DNA sequences, and to a process for screening 

potential cancer therapeutics meet the threshold test for 

patent-eligible subject matter under 35 U.S.C. § 101 in 

light of various Supreme Court holdings, particularly 

including Mayo. The issue is patent eligibility, not patentability. 

We would further note, in the context of discussing 

what this case is not about, that patents on life-saving 

material and processes, involving large amounts of risky 

investment, would seem to be precisely the types of subject matter that should be subject to the incentives of 

exclusive rights. But disapproving of patents on medical 

methods and novel biological molecules are policy questions best left to Congress, and other general questions 

relating to patentability and use of patents are issues not 

before us. As will be seen, on the limited questions before 

us, we conclude that the composition claims and the 

screening claim involving growing a transformed host cell 

meet the standards for patent eligibility, while the 

claimed methods for “analyzing” or “comparing” do not. 

A. Composition Claims: Isolated DNA Molecules 

i. 

The principal claims of the patents before us on remand relate to isolated DNA molecules. Mayo does not 

control the question of patent-eligibility of such claims. 

They are claims to compositions of matter, expressly 

authorized as suitable patent-eligible subject matter in 

§ 101. As to those claims, the issue of patent-eligibility 

remains, as it was on the first appeal to this court, 

whether they claim patent-ineligible products of nature. 

We hold that they do not. The isolated DNA molecules 

before us are not found in nature. They are obtained in 
39 ASSOCIATION FOR MOLECULAR v. PTO

the laboratory and are man-made, the product of human 

ingenuity. While they are prepared from products of 

nature, so is every other composition of matter. All new 

chemical or biological molecules, whether made by synthesis or decomposition, are made from natural materials. 

For example, virtually every medicine utilized by today’s 

medical practitioners, and every manufactured plastic 

product, is either synthesized from natural materials 

(most often petroleum fractions) or derived from natural 

plant materials. But, as such, they are different from 

natural materials, even if they are ultimately derived 

from them. The same is true of isolated DNA molecules. 

ii. 

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 “markedly different” from naturally occurring ones; and (2) 

incorrectly focusing not on the differences between isolated and native DNAs, but on one similarity: their informational content. Rather, Myriad argues, an isolated 

DNA molecule is patent eligible because it is, as claimed, 

“a nonnaturally occurring manufacture or composition of 

matter” with “a distinctive name, character, and use.” 

Appellants’ Br., 2010 WL 4600106, at 41-42 (quoting 

Chakrabarty, 447 U.S. at 309-10). Myriad contends that 

isolated DNA does not exist in nature and that isolated 

DNAs, unlike native DNAs, can be used as primers and 

probes for diagnosing cancer. Moreover, Myriad asserts 

that an ultimately-derived-from “products of nature” 

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 
ASSOCIATION FOR MOLECULAR v. PTO 40

precedents, the PTO’s 2001 Utility Examination Guidelines, and Congress’s role in enacting the patent laws. 

Regarding Mayo, Myriad argues that the Supreme Court’s 

decision did not address or alter the established patenteligibility test for composition claims, such that the standards announced in Chakrabarty still govern this appeal. 

To the extent that the general principles discussed in 

Mayo bear on the DNA claims, Myriad maintains that 

isolated DNA represents a nonnatural, man-made invention distinct from the lack of human ingenuity underlying 

the method claims there at issue. 

Plaintiffs respond that claims to isolated DNA molecules fail to satisfy § 101 because such claims cover natural 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 distinctive name, character, and use, making it “markedly 

different” from the natural product. In this case, Plaintiffs conclude that because isolated DNAs retain part of

the same nucleotide sequence as native DNAs, they do not 

have any “markedly different” characteristics. Furthermore, according to Plaintiffs, the isolated DNA claims 

preempt products and laws of nature, excluding anyone 

from working with the BRCA genes and the genetic 

information they convey. Under Mayo, Plaintiffs assert 

that any structural differences relative to the chromosomal BRCA genes do not add “enough” to the underlying 

natural genetic sequences to render Myriad’s isolated 

DNA molecules patentable under § 101. 

The government as amicus curiae does not defend the 

longstanding position of the PTO, a government agency, 

that isolated DNA molecules are patent eligible, arguing 
41 ASSOCIATION FOR MOLECULAR v. PTO

instead for a middle ground. Specifically, the government 

argues that DNA molecules engineered by man, including 

cDNAs,9 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 the first oral argument, the government illustrated 

its position by way of a so-called “magic microscope” test 

(an invention in and of itself, although probably not 

patent-eligible). Oral Arg. at 46:50-47:50. According to 

the government’s test then, if an imaginary microscope 

could focus in on the claimed DNA molecule as it exists in 

the human body, the claim covers ineligible subject matter. The government thus argued 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 sequences are not patent eligible. 

In contrast, the government contended, because an 

imaginary microscope could not focus in vivo on a cDNA 

sequence, which is engineered by man to splice together 

non-contiguous coding sequences (i.e., exons), claims 

covering cDNAs are patent eligible. 

In sum, although the parties and the government appear 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. 

 9 According to the government, several of the composition claims at issue in this suit, including claim 2 of 

the ’282 patent, are limited to cDNA and thus patent 

eligible. We agree. 
ASSOCIATION FOR MOLECULAR v. PTO 42

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. 

iii. 

While Mayo and earlier decisions concerning method 

claim patentability provide valuable insights and illuminate broad, foundational principles, the Supreme Court’s 

decisions in Chakrabarty and Funk Brothers set out the 

primary framework for deciding the patent eligibility of 

compositions of matter, including isolated DNA molecules.10

In Chakrabarty, the Court addressed the question 

whether a man-made, living microorganism is a patent-

 10 Other Supreme Court decisions cited by the parties and amici relating to patented manufactures and 

compositions of matter were decided based on lack of 

novelty, not patent-eligible 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 various 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 Cochrane 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 preparing 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 is to be the subject of the patent, 

and is the process of preparing the known product alizarine from anthracine.” (emphases added)). 
43 ASSOCIATION FOR MOLECULAR v. PTO

eligible manufacture or composition of matter within the 

meaning of § 101. 447 U.S. at 305, 307. The microorganisms 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 significant use in more efficiently treating oil spills. Id. at 305, 

305 n.2. The Court held that the bacteria qualified as 

patent-eligible subject matter because the “claim is not to 

a hitherto unknown natural phenomenon, but to a nonnaturally occurring manufacture or composition of matter—a product of human ingenuity ‘having a distinctive 

name, character [and] use.’” Id. at 309-10 (quoting Hartranft v. Wiegmann, 121 U.S. 609, 615 (1887)). 

To underscore the point, the Court compared Chakrabarty’s engineered bacteria with the mixed bacterial 

cultures found unpatentable in Funk Brothers, again 

casting this case, more relating to 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 leguminous plants do not mutually inhibit 

each other. 333 U.S. at 129-30. Based on that discovery, 

the patentee produced (and claimed) mixed cultures of 

nitrogen-fixing species capable of inoculating a broader 

range of leguminous plants than single-species cultures. 

Id. The Court held that the bacteria’s cooperative qualities were, “like the heat of the sun, electricity, or the 

qualities of metals,” the “work of nature,” and thus not 

patentable. Id. at 130. The Court also held that applying 

the newly discovered bacterial compatibility to create a 

mixed culture was not a patentable advance because no 

species acquired a different property or use. Id. at 131. 
ASSOCIATION FOR MOLECULAR v. PTO 44

The Chakrabarty Court thus concluded that what distinguished Chakrabarty’s oil-degrading bacteria from the 

mixed cultures 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. Chakrabarty, 447 U.S. at 310. 

One distinction, therefore, between products of nature 

and 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 

arrayed in useful combinations or harnessed to exploit 

newly discovered properties, have similar characteristics 

as in nature, and compositions that human intervention 

has given “markedly different,” or “distinctive,” characteristics. Id. (citing 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, the 

challenged claims are drawn to patent-eligible subject 

matter because the claims cover molecules that are markedly different—have a distinctive chemical structure and 

identity—from those found in nature. 

It is undisputed that Myriad’s claimed isolated DNAs 

exist in a distinctive chemical form—as distinctive chemical molecules—from DNAs in the human body, i.e., native 

DNA. Natural DNA exists in the body as one of forty-six 

large, contiguous DNA molecules. Each of those DNA 

molecules is condensed and intertwined with various 

proteins, including histones, to form a complex tertiary 

structure known as chromatin that makes up a larger 

structural complex, a chromosome. See supra, Figure 3. 

Inside living cells, the chromosomes are further encapsulated within a series of membranes and suspended in a 

complex intracellular milieu.
45 ASSOCIATION FOR MOLECULAR v. PTO

Isolated DNA, in contrast, is a free-standing portion of 

a larger, natural DNA molecule. 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 approximately 10,200 

nucleotides and BRCA1 to just around 5,500 nucleotides. 

Furthermore, claims 5 and 6 of the ’282 patent cover 

isolated DNAs, e.g., primers or probes, having as few as 

fifteen nucleotides of a BRCA sequence. Accordingly, 

BRCA1 and BRCA2 in their isolated states are different 

molecules from DNA that exists in the body; isolated DNA 

results from human intervention to cleave or synthesize a 

discrete portion of a native chromosomal DNA, imparting 

on that isolated DNA a distinctive chemical identity as 

compared to native DNA. 

As the above description indicates, isolated DNA is 

not just purified DNA. Purification makes pure what was 

the same material, but was combined, or contaminated, 

with other materials. Although isolated DNA is removed 

from its native cellular and chromosomal environment, it 

has also been manipulated chemically so as to produce a 

molecule that is markedly different from that which exists 

in the body. 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, 

albeit being “for every practical purpose a new thing 

commercially and therapeutically.” 189 F. 95, 103 

(C.C.S.D.N.Y. 1911). Judge Learned Hand’s opinion for 
ASSOCIATION FOR MOLECULAR v. PTO 46

the district court in that oft-cited case held the purified 

“Adrenalin” to be patent-eligible subject matter. Id. The 

In re Marden cases are similarly inapposite, directed as 

they are to the patent ineligibility of purified natural 

elements—ductile uranium, 47 F.2d 957 (CCPA 1931), 

and vanadium, 47 F.2d 958 (CCPA 1931)—that are inherently ductile in purified form. While purified natural 

products thus may or may not qualify for patent under 

§ 101, the isolated DNAs of the present patents constitute 

an a fortiori situation, where they are not only purified; 

they are different from the natural products in “name, 

character, and use.” Chakrabarty, 447 U.S. at 309-10.11 

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 

 11 In re Bergy, relating to a purified microorganism, 

596 F.2d 952, 967-68 (CCPA 1979), was once a companion 

case to Chakrabarty but was vacated by the Supreme 

Court and remanded for dismissal as moot when the 

inventors withdrew their claim from the pending application. 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 compounds, 

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 

nonobvious claims to synthetically produced, substantially pure 2-methyl-2-pentenoic acid, 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 invalid 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 impurities invalid as 

not “inventive,” and thus obvious). 
47 ASSOCIATION FOR MOLECULAR v. PTO

isolated DNA molecules do not exist in nature within a 

physical mixture to be purified. They have to be chemically cleaved from their native chemical combination with 

other genetic materials. In other words, in nature, the 

claimed isolated DNAs are covalently bonded to such 

other materials. Thus, when cleaved, an isolated DNA 

molecule is not a purified form of a natural material, but 

a distinct chemical entity that is obtained by human 

intervention. See Chakrabarty, 447 U.S. at 313 (“the 

relevant distinction [is] between products of nature . . . 

and human-made inventions”). In fact, some forms of 

isolated DNA may require no purification at all, because 

DNAs can be chemically synthesized directly as isolated 

molecules. 

The above analysis holding the isolated DNA molecules to be patent-eligible subject matter applies to all of 

the asserted composition claims on appeal in this case. 

However, as the government has pointed out, claim 2 of 

the ’282 patent is narrower than claim 1 and reads only 

on cDNAs, which lack the non-coding introns present in 

the genomic BRCA1 gene.12 While, as we have held, all of 

the claimed isolated DNAs are eligible for patent as 

compositions of matter distinct from natural DNA, the 

claimed cDNAs are especially distinctive, lacking the noncoding introns present in naturally occurring chromosomal DNA. They are even more the result of human 

intervention into nature and are hence patent-eligible 

subject matter. The government, as noted earlier, has 

agreed with that conclusion. Br. United States, 2010 WL 

4853320, at 14-17.

The dissent disparages the significance of a “chemical 

bond,” presumably meaning a covalent bond, in distin-

 12 Claims 2 and 7 of the ’282 patent and claim 7 of 

the ’492 patent recite isolated cDNA molecules. 
ASSOCIATION FOR MOLECULAR v. PTO 48

guishing structurally between one molecular species and 

another. But a covalent bond is the defining boundary 

between one molecule and another, and 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 connect 

different chemical moieties to one another. 

Plaintiffs argue that because the claimed isolated 

DNAs retain the same nucleotide sequence as native 

DNAs, they do not have any “markedly different” characteristics. 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, albeit 

a key one: the information content contained in isolated 

and native DNAs’ nucleotide sequences. 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 nonobviousness 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. The 

claimed isolated DNA molecules are distinct from 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 patents by their structures rather than by their functions. In 
49 ASSOCIATION FOR MOLECULAR v. PTO

fact, many different materials may have the same function (e.g., aspirin, ibuprofen, and naproxen). 

The district court in effect created a categorical rule 

excluding isolated genes from patent eligibility. See SJ 

Op., 702 F. Supp. 2d 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 legislature has not expressed,’” Bilski, 130 S. 

Ct. at 3226 (quoting Diehr, 450 U.S. at 182), 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). Contrary to the conclusions 

of the district court and the suggestions of Plaintiffs and 

some amici, § 101 applies equally to all putative inventions, and isolated DNA is not and should not be considered a special case for purposes of patent eligibility under 

existing law. See, e.g., SJ Op., 702 F. Supp. 2d at 185 

(“DNA represents the physical embodiment of biological 

information, distinct in its essential characteristics from 

any other chemical found in nature.”); Appellees’ Suppl. 

Br. at 4-5 (“Unlike other chemicals, the information 

encoded by DNA reflects its primary biological function . . 

. .”). 

Under the statutory rubric of § 101, isolated DNA is a 

tangible, man-made composition of matter defined and 

distinguished by its objectively discernible chemical 

structure. Whether its unusual status as a chemical 

entity that conveys genetic information warrants singular 

treatment under the patent laws as the district court did 

is a policy question that we are not entitled to address. 

Cf. Nat’l Fed’n of Indep. Bus. v. Sebelius, 132 S. Ct. 2566, 

slip op. at 6 (2012) (“[W]e possess neither the expertise 

nor the prerogative to make policy judgments. Those 
ASSOCIATION FOR MOLECULAR v. PTO 50

decisions are entrusted to our Nation’s elected leaders, 

who can be thrown out of office if the people disagree with 

them.”). Congress is presumed to have been aware of the 

issue, having enacted a comprehensive patent reform act 

during the pendency of this case, and it is ultimately for 

Congress if it wishes to overturn case law and the long 

practice of the PTO to determine that isolated DNA must 

be treated differently from other compositions of matter to 

account for its perceived special function. We therefore 

reject the district court’s unwarranted categorical exclusion of isolated DNA molecules. 

Because isolated DNAs, not just cDNAs, have a markedly different chemical structure compared to native 

DNAs, we reject the government’s earlier proposed “magic 

microscope” 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 government’s microscope could focus in on a claimed 

portion of any complex molecule, rendering that claimed 

portion 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 containing 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. 
51 ASSOCIATION FOR MOLECULAR v. PTO

The Supreme Court in Mayo focused on its concern 

that permitting patents on particular subject matter 

would prevent use by others of, in Mayo, the correlation 

recited in the method claims. Plaintiffs argue here that 

they are preempted from using the patented DNA molecules. The answer to that concern is that permitting 

patents on isolated genes does not preempt a law of 

nature. A composition of matter is not a law of nature. 

Moreover, as indicated earlier, a limited preemption is 

inherent in every patent: the right to exclude for a limited 

period of time. 35 U.S.C. § 154(a)(1) (“Every patent shall 

contain . . . a grant to the patentee, his heirs or assigns, of 

the right to exclude others from making, using, offering 

for sale, or selling the invention throughout the United 

States . . . .”). When the patent expires, the public is 

entitled to practice the invention of the patent. That is 

true of all inventions; during the term of the patent, 

unauthorized parties are “preempted” from practicing the 

patent, but only for its limited term. The seven patents 

being challenged here all expire by December 18, 2015.13 

Any preemption thus is limited, very limited in the case of 

the present patents. Moreover, patents are rarely enforced against scientific research, even during their terms. 

The remand of this case for reconsideration in light of 

Mayo might suggest, as Plaintiffs and certain amici state, 

that the composition claims are mere reflections of a law 

of nature. Respectfully, they are not, any more than any 

product of man reflects and is consistent with a law of 

nature. Everything and everyone comes from nature, 

following its laws. But the compositions here are not 

 13 Specifically, the ’441 patent will expire on August 

12, 2014; the ’473 patent will expire on December 2, 2014; 

the ’999 and ’001 patents will expire on January 20, 2015; 

the ’282 patent will expire on May 5, 2015; and the ’492 

and ’857 patents will expire on December 18, 2015. 
ASSOCIATION FOR MOLECULAR v. PTO 52

natural products. They are the products of man, albeit 

following, as all materials do, laws of nature. 

The dissent indicates that “elemental lithium (like 

other elements) would not be patentable subject matter, 

even if it could only be extracted from nature through an 

isolation process.” But the isolation here is not a simple 

separation from extraneous materials, but conversion to a 

different molecular entity. And again, these facts are not 

before us, so we do not attempt to evaluate the patentability of one form of lithium over another. Courts decide 

cases; they do not draft comprehensive legal treatises. 

Suffice it to say, however, that if lithium is found in the 

earth as other than elemental lithium because it reacts 

with air and water to form, for example, lithium oxide or 

lithium hydroxide, it is a different material. A lithium 

compound is not 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, 

easily done by anyone. Creating a new chemical entity is 

the work of human transformation, requiring skill, 

knowledge, and effort. See Mayo, 132 S. Ct. at 1294 

(“While a scientific truth . . . is not a patentable invention, 

a novel and useful structure created with the aid of 

knowledge of scientific truth may be.”) (quoting Mackay 

Radio & Tel. Co. v. Radio Corp. of Am., 306 U.S. 86, 94 

(1939)). 

The dissent also mentions several times in its opinion 

the “breathtaking[]” breadth of certain claims as grounds 

for objecting to their patentability. However, we do not 
53 ASSOCIATION FOR MOLECULAR v. PTO

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 under § 101, not 

the adequacy of the patents’ disclosure to support particular claims. Nor is it lack of patentability for obviousness, 

as the dissent intimates, that is before us. 

The dissent finally attempts to analogize the creation 

of the isolated DNAs in this case to the removal of a 

kidney from the human body, indicating that the latter 

does not create patent-eligible subject matter, hence the 

claimed isolated DNAs also do not. Such an analogy is 

misplaced. Extracting a kidney from a body does not 

result in a patent-eligible composition, as an isolated gene 

has been and should be. A kidney is an organ, not a well 

defined composition of matter or an article of manufacture 

specified by § 101. No one could confuse extensive research needed to locate, identify, and isolate a gene with 

the extraction of an organ from a body. One is what 

patents are intended to stimulate research on and hence 

are properly patent eligible, and the other, while obviously essential to human wellbeing, is not what patents 

are understood to cover under the patent statute. An 

isolated DNA is properly characterized as a composition of 

matter under § 101; no one would so characterize an 

isolated body organ. 

Finally, our decision that isolated DNA molecules are 

patent eligible comports with the longstanding practice of 

the PTO and the courts. The Supreme Court has repeatedly stated that changes to longstanding practice should 

come from Congress, not the courts. In J.E.M. Ag Supply, 

Inc. v. Pioneer Hi-Bred International, Inc., the Court 

rejected the argument 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 Con-
ASSOCIATION FOR MOLECULAR v. PTO 54

gress or agencies with expertise that such coverage is 

inconsistent with [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 adopting 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 Pharms., Inc. v. Eli Lilly & Co., 

598 F.3d 1336, 1347 (Fed. Cir. 2010) (en banc) (upholding 

a written description requirement separate from enablement based in part on stare decisis). 

In this case, the PTO has issued patents relating 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 estimated 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 relating to, in non-native form, 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 and 

investing communities, the decision must come, not from 

the courts, but from Congress. The dissent mentions 

possible “adverse effects” that may occur if isolated DNAs 

are held to be patent eligible. But, respectfully, it is the 

adverse effects on innovation that a holding of ineligibility 

might cause. Patents encourage innovation and even 
55 ASSOCIATION FOR MOLECULAR v. PTO

encourage inventing around; we must be careful not to 

rope off far-reaching areas of patent eligibility. 

Accordingly, we once again conclude that claims 1, 2, 

5, 6, and 7 of the ’282 patent; claims 1, 6, and 7 of the ’492 

patent; and claim 1 of the ’473 patent directed to isolated 

DNA molecules recite patent-eligible subject matter under 

§ 101. Mayo does not change that result. In so doing, we 

reiterate that the issue before us is patent eligibility, not 

patentability, about which we express no opinion. 

II. Method Claims 

We turn next to Myriad’s challenged method claims. 

This court in its now-vacated decision of July 29, 2011, 

had held method claims 1 of the ’999, ’001, and ’441 

patents, as well as method claims 1 and 2 of the ’857 

patent—all of which consist of analyzing and comparing 

certain DNA sequences—not to be patent-eligible subject 

matter on the ground that they claim only abstract mental processes. In light of the Supreme Court’s decision in 

Mayo, we reaffirm that prior holding. The Court made 

clear that such diagnostic methods in that case essentially 

claim natural laws that are not eligible for patent. Without expressly analyzing the instant method claims in the 

context of the Court’s reasoning, but in light of the Court’s 

holding, and in view of our own prior reasoning, set forth 

herein below, those method claims cannot stand. 

In our prior decision, however, we reversed the district court’s holding that claim 20 of the ’282 patent was 

not eligible for patent. We did so on the ground, inter

alia, that, in addition to the step of comparing the cells’ 

growth rates, the claim also recites the steps of growing 

transformed cells and determining those growth rates. 

We relied on the fact that those steps were transformative. Although the Court has now held that certain transformative steps are not necessarily sufficient under § 101 
ASSOCIATION FOR MOLECULAR v. PTO 56

if the recited steps only rely on natural laws, we once 

again, even in light of Mayo, arrive at the same conclusion 

of patent-eligibility because at the heart of claim 20 is a 

transformed cell, which is made by man, in contrast to a 

natural material. 

A. Methods of “Comparing” or “Analyzing” Sequences 

Myriad argued that its claims to methods of “comparing” or “analyzing” BRCA sequences satisfy the machineor-transformation test because each requires a transformation—extracting and sequencing DNA molecules from 

a human sample—before the sequences can be compared 

or analyzed. According to Myriad, the district court failed 

to recognize the transformative nature of the claims by (1) 

misconstruing the claim term “sequence” as merely information, rather than a physical molecule; and (2) erroneously concluding, in the alternative, that Myriad’s 

proposed transformations were mere data-gathering 

steps, rather than central to the purpose of the claims. 

Plaintiffs responded that these method claims are 

drawn to the abstract idea of comparing one sequence to a 

reference sequence and preempt a phenomenon of nature—the correlation of genetic mutations with a predisposition 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 renew our conclusion that Myriad’s claims to 

“comparing” or “analyzing” two gene sequences fall outside the scope of § 101 because they claim only abstract 

mental processes. See Benson, 409 U.S. at 67 (“Phenomena of nature, . . . mental processes, and abstract intellec-
57 ASSOCIATION FOR MOLECULAR v. PTO

tual 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 nontumor 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: one looks at the first position in a first 

sequence; determines the nucleotide sequence at that first 

position; looks at the first position in a second sequence; 

determines the nucleotide sequence at that first position; 

determines 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 alteration; and repeats the process 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 patenteligible subject matter, id. at 3230, Myriad’s claims do not 

apply the step of comparing two nucleotide sequences in a 

process. Rather, the step of comparing two DNA sequences is the entire process that is claimed. 
ASSOCIATION FOR MOLECULAR v. PTO 58

To avoid this result, Myriad attempts to read into its 

method claims additional, allegedly transformative steps. 

As described above, Myriad reads into its claims the steps 

of (1) extracting DNA from a human sample, and (2) 

sequencing 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 sampleprocessing 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 such meaning when read in light of the patent specifications. Specifically, Myriad argues that the specifications 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. That may be true, but the claims only recite 

mental steps, not the structure of physical DNA molecules. 

Accordingly, Myriad’s challenged method claims are 

indistinguishable from the claims the Supreme Court 

found invalid under § 101 in Mayo. In Mayo, the patents 

claimed methods for optimizing the dosage of thiopurine 

drugs administered to patients with gastrointestinal 

disorders. 132 S. Ct. at 1295. As written, the claimed 

methods included the steps of (a) “administering” a thiopurine drug to a subject, and/or (b) “determining” the 

drug’s metabolite levels in the subject, wherein the measured metabolite levels are compared with predetermined 

levels to optimize drug dosage. Id. In holding that the 
59 ASSOCIATION FOR MOLECULAR v. PTO

claims satisfied § 101, this court concluded that, in addition to the “administering” step being transformative, the 

“determining” step was both transformative and central 

to the purpose of the claims. Prometheus, 628 F.3d at 

1357. However, the Supreme Court held that the steps of 

administering and determining, combined with a correlative “wherein” clause, were not sufficiently transformative 

of what was otherwise a claim to a natural law. That 

holding governs Myriad’s claims to methods of “comparing” and “analyzing” DNA sequences. 

Myriad’s other claims do not even include a Mayo-like

step of “determining” the sequence of BRCA genes by, e.g., 

isolating the genes from a blood sample and sequencing 

them, or any other putatively transformative step. 

Rather, the comparison between the two sequences can be 

accomplished by mere inspection alone. Accordingly, 

Myriad’s claimed methods of comparing or analyzing 

nucleotide sequences are only directed to the abstract 

mental process of comparing two nucleotide sequences. 

As such, we hold claims 1 of the ’999 patent, ’001 patent, 

and ’441 patent and claims 1 and 2 of the ’857 patent 

invalid under § 101 for claiming patent-ineligible processes. 

B. Method of Screening Potential Cancer Therapeutics 

Lastly, we turn to claim 20 of the ’282 patent, directed 

to a method for screening potential cancer therapeutics 

via changes in cell growth rates of transformed cells. The 

parties agree that those transformed cells arose from 

human effort; i.e., they are not natural products. Plaintiffs nonetheless challenge claim 20 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 
ASSOCIATION FOR MOLECULAR v. PTO 60

a cancer therapeutic. Plaintiffs therefore contend that 

claim 20 is indistinguishable from the claims held ineligible in Mayo. We disagree. 

Claim 20 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. Claim 20 

thus recites a screening method premised on the use of 

“transformed” host cells. Those cells, like the patenteligible cells in Chakrabarty, are not naturally occurring. 

Rather, they are derived by altering a cell to include a 

foreign gene, resulting in a man-made, transformed cell 

with enhanced function and utility. See ’282 patent col.27 

ll.28-33. The claim thus includes more than the abstract 

mental step of looking at two numbers and “comparing” 

two host cells’ growth rates. 

In Mayo, the Supreme Court invalidated claims directed to the relationship between concentrations of 

certain metabolites in the blood and the likelihood that a 

particular dosage of a thiopurine drug will be optimum, 

stating that steps of “administering” and “determining,” 

coupled with a correlative “wherein” clause, were insufficient to differentiate the claimed method from the natural 

laws encompassed by the claims. In short, “to transform 

an unpatentable law of nature into a patent-eligible 

application of such a law, one must do more than simply 

state the law of nature while adding the words ‘apply it’.” 

132 S. Ct. at 1294. 

Here, claim 20 does do more; it does not simply apply 

a law of nature. Of course, all activity, whether chemical, 

biological, or physical, relies on natural laws. But, more 

to the point here is that claim 20 applies certain steps to 
61 ASSOCIATION FOR MOLECULAR v. PTO

transformed cells that, as has been pointed out above, are 

a product of man, not of nature. The Court, in its evaluation of the Mayo method claims, found that the additional 

steps of those claims were not sufficient to “transform” the 

nature of the claims from mere expression of natural laws 

to patent-eligible subject matter. By definition, however, 

performing operations, even known types of steps, on, or 

to create, novel, i.e., transformed subject matter is the 

stuff of which most process or method invention consists. 

All chemical processes, for example, consist of hydrolyzing, hydrogenating, reacting, etc. In situations where the 

objects or results of such steps are novel and nonobvious, 

they should be patent-eligible. It is rare that a new 

reaction or method is invented; much process activity is to 

make new compounds or products using established 

processes. Thus, once one has determined that a claimed 

composition of matter is patent-eligible subject matter, 

applying various known types of procedures to it is not 

merely applying conventional steps to a law of nature. 

The transformed, man-made nature of the underlying 

subject matter in claim 20 makes the claim patenteligible. The fact that the claim also includes the steps of 

determining the cells’ growth rates and comparing growth 

rates does not change the fact that the claim is based on a 

man-made, non-naturally occurring transformed cell—

patent-eligible subject matter. 

Furthermore, 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. 

Accordingly, we hold that claim 20 of the ’282 patent 

recites patent-eligible subject matter under § 101. 

Whether such processes, including claim 20, meet other 
ASSOCIATION FOR MOLECULAR v. PTO 62

tests for patentability, such as novelty or nonobviousness, 

is not before us. 

CONCLUSION

For the foregoing reasons, we affirm the district 

court’s decision to exercise declaratory judgment jurisdiction over this case, we reverse the district court’s grant of 

summary judgment with regard to Myriad’s composition 

claims to isolated DNAs, including cDNAs, we affirm the 

district court’s grant of summary judgment with regard to 

Myriad’s method claims directed 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 screening potential cancer therapeutics 

via changes in cell growth rates of novel, man-made 

transformed cells. 

AFFIRMED IN PART and REVERSED IN PART 

COSTS

Costs to Myriad. 
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 

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, 
ASSOCIATION FOR MOLECULAR v. PTO 2

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 join 

the majority with respect to claims to isolated cDNA 

sequences, and concur in the judgment with respect to 

isolated DNA sequences. I write separately to explain my 

reasoning. 

I. 

The Patent Act, 35 U.S.C. § 101, allows “[w]hoever invents 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 

“process, machine, manufacture, or composition of matter.” “Congress intended statutory subject matter to 

‘include anything under the sun that is made by man.’” 

Diamond v. Chakrabarty, 447 U.S. 303, 309 (1980) (quoting the statutory history). 

While the plain language used by Congress did not 

limit the scope of patentable subject matter in the statute, 
3 ASSOCIATION FOR MOLECULAR v. PTO

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, 3226 (2010) (quoting Chakrabarty, 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 protect.” Parker v. Flook, 437 U.S. 584, 593 (1978). 

Applying the judicially created exception to the otherwise 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) (Frankfurter, J., concurring) (“[S]uch terms as ‘the work of 

nature’ and the ‘laws of nature’ . . . are vague and malleable . . . . Arguments drawn from such terms for ascertaining 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. Chakrabarty, 447 U.S. at 309. 

Even when an invention does not exist in nature in 

the claimed state, it may still be directed to subject matter that is not patentable. 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 “acquire[ed] a different use” 

in combination. Funk Bros., 333 U.S. at 131-32. The 

aggregation of the bacterial strains into a single product 
ASSOCIATION FOR MOLECULAR v. PTO 4

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 included extra genetic material introduced by the inventor 

were “a nonnaturally occurring manufacture or composition 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)). Chakrabarty 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” because “‘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 

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 patentable 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. 
5 ASSOCIATION FOR MOLECULAR v. PTO

Funk Brothers indicates that an invention which “serve[s] 

the ends nature originally provided” is likely unpatentable 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 distinctive name, character, and use, e.g., markedly different 

characteristics with the potential for significant utility, is 

patentable subject matter. 447 U.S. at 309-10. Although 

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 adrenaline 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 principle” the resulting purified adrenaline was “for every 

practical purpose a new thing commercially and therapeutically.” Id. Similarly, in a case applying the Patent 

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 Mathieson 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-

 1 The Patent Act of 1952 was the first time patentable 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. 
ASSOCIATION FOR MOLECULAR v. PTO 6

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 produced 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.”); 

In re Marden, 47 F.2d 957 (CCPA 1931) (“ductile uranium” 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. General 

Electric 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 
7 ASSOCIATION FOR MOLECULAR v. PTO

Chakrabarty, the claims all fell within the laws of nature 

exception. 

As illustrated by these examples, courts have long applied 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. 

II. 

We reconsider whether the claims at issue in this case 

are directed to patentable subject matter following the 

remand from the Supreme Court in light of its opinion in 

Mayo Collaborative Services v. Prometheus Laboratories, 

Inc., 132 S. Ct. 1289 (2012) (Prometheus). While the 

Prometheus decision does not control the outcome in this 

case, it is nonetheless instructive regarding the scope of 

the law of nature exception. As an initial matter, the 

Prometheus discussion of laws of nature (process claims) 

clearly ought to apply equally to manifestations of nature 

(composition claims). Myriad’s argument that Prometheus is constrained to methods is an untenable position. 

As the Prometheus court explained: “If a law of nature 

is not patentable, then neither is a process reciting a law 

of nature, unless that process has additional features that 

provide practical assurance that the process is more than 

a drafting effort designed to monopolize the law of nature 

itself.” Id. at 1297. Prometheus did not, however, overturn Funk Brothers or Chakrabarty; cases clearly more 

analogous to the one before us. Using the framework of 

Funk Brothers and Chakrabarty in conjunction with the 

direction of Prometheus, the applicable principles are: (1) 

laws of nature/manifestations of nature are not patentable; (2) a composition of matter with “markedly 

different characteristics” from that found in nature with 
ASSOCIATION FOR MOLECULAR v. PTO 8

the potential for significant utility is directed to patentable subject matter. 

Does the isolation process change the DNA from an 

unpatentable manifestation of nature into a patentable 

composition of matter? Id. at 1299. Does the claimed 

isolated DNA 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. 

The isolated DNA claims of the patents in suit fall 

into two categories. The first category of claims is directed to isolated sequences that are identical to naturally 

occurring gene sequences. These include claims encompassing both the isolated full length gene sequence (e.g. 

claim 1 of ’282 patent), which are thousands of nucleotides, 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. Although 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, 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, 
9 ASSOCIATION FOR MOLECULAR v. PTO

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 nucleotides, 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 

other things, greater stability for the DNA sequence as 

compared to the RNA sequence. 

cDNA sequences thus have a distinctive character and 

use, with markedly different chemical characteristics 

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 reserved 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 cDNA, 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, the isolated 

 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. 
ASSOCIATION FOR MOLECULAR v. PTO 10

DNA claims include nucleotide sequences which are found 

in the human body, albeit as part of a much larger molecule, the chromosome. To the extent the majority rests its 

conclusion on the chemical differences between genomic 

and isolated DNA (breaking the covalent bonds), I cannot 

agree that this is sufficient to hold that the claims to 

human genes are directed to patentable subject matter. I 

agree that isolated genes are a different molecule and are 

therefore not squarely analogous to unpatentable minerals, created by nature without the assistance of man. 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. 

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 ranging 

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 screening process to detect gene mutations. These smaller 

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 do this. 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 
11 ASSOCIATION FOR MOLECULAR v. PTO

the range of . . . utility” as compared to nature. Funk 

Bros., 333 U.S. at 131. In Prometheus, the Supreme 

Court held that the claims at issue were not directed to 

patentable subject matter because they merely “set forth 

laws of nature—namely, relationships between concentrations of certain metabolites in the blood and the likelihood 

that a dosage of a thiopurine drug will prove ineffective or 

cause harm.” 132 S. Ct. at 1296-97. The claimed relationship was “a consequence of the ways in which thiopurine compounds are metabolized by the body—entirely 

natural processes.” Id. at 1297. 

There is no suggestion that the human body naturally 

uses 15-mers as primers to synthesize DNA, or that the 

attendant process of “probing” a patient’s DNA to detect a 

mutation is somehow a natural law. The ability to use a 

short strand of DNA as a primer or probe to determine 

whether a patient has a mutation is a new and important 

utility substantially different from the role of that DNA as 

it occurs in nature. Indeed, many of the plaintiffs in this 

case submitted declarations indicating that they wanted 

to either offer such testing or receive such testing. Unlike 

Prometheus, the claims to short isolated strands of DNA 

are not directed to the relationship between the mutation 

and cancer, but rather to a new tool that can be used to 

determine if that relationship exists. The short isolated 

DNA sequences have markedly different properties which 

are directly responsible for their new and significant 

utility. Chakrabarty, 447 U.S. at 309-10. It is not the 

chemical change alone, but that change combined with 

the different and beneficial utility that leads me to conclude that small isolated DNA fragments are patentable 

subject matter. Id. at 310. 

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-
ASSOCIATION FOR MOLECULAR v. PTO 12

eligible subject matter. The dissent explains why the 

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, and he has molded the 

retained portion into a product that bears little resemblance to that which occurs naturally.” Dissent at 11-12. 

The exact same thing is true with regard to primer and 

probe claims. Man has whittled the chromosomal DNA 

molecule down to a 15 nucleotide sequence – defining the 

parts to be retained and discarded.3 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.4 

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.” 447 U.S. at 310. 

Turning now to the longer strands of isolated DNA, 

isolated strands which include most or all of the gene 

present a more difficult case. Some of the claims at issue, 

for example ’282 patent claim 5, are genus claims, drafted 

 3 If adding functionality to a naturally occurring 

molecule, for example adding a lipid chain, is a creation of 

man then removing functionality, for example truncating 

a natural DNA sequence or protein to yield smaller molecules with new properties should also be. 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 Chapel, created by adding 

layers of paint to an existing structure. 

4 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? 
13 ASSOCIATION FOR MOLECULAR v. PTO

broadly enough to include both short fragments as well as 

the entire isolated gene sequence. While I ultimately 

conclude that these longer isolated sequences, 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 chemical difference from the gene as it appears on the chromosome. 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.”). The isolated full length gene does not clearly have a new utility 

and appears to simply serve the same ends devised by 

nature, namely to act as a gene encoding a protein sequence. 

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. The 

scope of the law of nature/manifestation of nature exception was certainly enlarged in Prometheus. But we do not 

decide this case on a blank canvas. 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 
ASSOCIATION FOR MOLECULAR v. PTO 14

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.5 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.6

III. 

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 

 5 See, e.g., U.S. Patent 3,067,099 (claiming vancomycin, an antibiotic produced by bacteria found in soil) 

and U.S. Patent 4,552,701 (claiming a vancomycin fragment produced by removing a sugar unit). A natural 

product fragment, for example a naturally occurring 

antibiotic with a sugar moiety removed, is highly analogous 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). 

6 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 

small number of chromosomes as compared to the number 

of genes. 
15 ASSOCIATION FOR MOLECULAR v. PTO

not occur in that isolated form in nature . . . .” 66 Fed. 

Reg. 1092, 1093 (Jan. 5, 2001). I do not agree with the 

dissent’s characterization of the PTO position as perfunctory. The PTO concluded that isolated DNA is patentable 

because it is different from what is found in nature – the 

process of synthesizing it or isolating it changes it. While 

the PTO lacks substantive rule making authority, it is not 

without expertise in this area. 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, it granted patents to human 

genes in the early 1980s, and subsequently issued thousands of patents on “isolated DNA.” Majority at 54. 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] purified 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 accounted for over 50% of Amgen’s revenue in 1997. Amgen, 

Inc. v. Hoechst Marion Roussel, Inc., 126 F.Supp.2d 69, 77 
ASSOCIATION FOR MOLECULAR v. PTO 16

(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 industry 

– 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 fundamental 

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 expectations 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.” Id. at 739. 

The settled expectations of the inventing community with 

respect to isolated DNA claims are built upon the broad 

language of the statute, judicial precedent, such as ParkeDavis and Merck, and the Patent Office’s longstanding 

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 

yet expired and which would be affected by our decision.’” 
17 ASSOCIATION FOR MOLECULAR v. PTO

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, now argues that 

the Patent Office’s published guidelines are incorrect and 

a misstatement of the law. In place of these guidelines, 

the government suggested that a “magic microscope” 

would provide a useful metaphor for guiding our section 

101 analysis. 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 “unisolated” sequence in the chromosome 

(the ends are different). 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 chromosome, the isolated fragment of DNA is 

a different molecule. Creating the claimed isolated DNA 

sequences therefore results in a distinctly unnatural 

molecule.7 Even the dissent agrees that the isolated DNA 

molecules at issue require cleaving chemical bonds, 

though it disputes the importance of the resulting distinct 

 7 This also illustrates why the government’s analogies to situations dealing with elements, for example 

lithium, are inapposite. Even assuming the government’s 

contention that lithium does not currently 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 

chromosomal DNA. Unlike a lithium salt, the chromosome does not imply that an isolated DNA molecule of 15 

nucleotides – or even a gene – necessarily previously 

existed as an isolated molecule in nature. 
ASSOCIATION FOR MOLECULAR v. PTO 18

“‘molecular species.’” Dissent at 7 (quoting Linus Pauling, 

The Nature of the Chemical Bond 6 (3d ed. 1960)). 

The dissent claims that the Patent Office’s past views 

are “substantially undermined by the position the government has taken in this case.” Dissent at 20. 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 government 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 

government argues in this case. Instead the government 

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 microorganisms, there is a clear difference between allowing additional patent protection where none previously existed, 

and denying patent protection decades (or centuries) after 

the fact, thereby eliminating a large number of property 

rights. Chakrabarty, consistent with the broad language 

of the statute, allowed additional patents where none 

previously existed. In contrast, the government 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 Congress. 

Nevertheless, the government 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 government 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 
19 ASSOCIATION FOR MOLECULAR v. PTO

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 

isolated portions of human DNA – the very thing that 

makes us humans, and not chimpanzees. 

The invitation is tempting, but I decline the opportunity to act where Congress has chosen not to. Congress 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.” 149 Cong. Rec. E2417-01. 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.8 Far from oblivious to the patenting of genes, 

Congress introduced and declined to pass several bills 

 8 “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 humans, 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.” 149 Cong. 

Rec. E2417-01 (emphasis added); see also 157 Cong. Rec. 

E1177-04 (resubmitting this testimony in the context of 

the current patent reform legislation). 
ASSOCIATION FOR MOLECULAR v. PTO 20

which would put a moratorium on gene patents,9 authorize funding for the study of whether genes ought to be 

patentable,10 and exempt from patent infringement 

anyone who uses patented genes for non-commercial 

research purposes or medical practitioners who use genetic diagnostic tests.11 Congress is obviously aware of 

the issues presented in this case and I believe “[a]ny recalibration of the standard of [patentability] remains in 

its hands.” Microsoft Corp. v. i4i Ltd., 131 S. Ct. 2238, 

2252 (2011). 

The judiciary cannot engage in an ad hoc innovationbased analysis, which is why the exceptions to patentability apply only to the clearest cases: a new mineral discovered in the earth, or a new plant found in the wild, or 

E=mc2, or the law of gravity. It is Congress, with “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 America v. Universal City 

Studios, Inc., 464 U.S. 417, 431 (1984), who must decide 

whether it is necessary to change the scope of section 101 

 9 At least one bill was introduced in Congress to put 

a moratorium on patents to human genes or gene sequences. See, e.g., The Animal and Gene Patent Moratorium Bill (S.387 1993). 

10 The Genomic Science and Technology Innovation 

Act of 2002 (H.R. 3966). 

11 The Genomic Research and Diagnostic Accessibility Act of 2002 (H.R. 3967). As the bill’s sponsor explained: “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. 
21 ASSOCIATION FOR MOLECULAR v. PTO

to exclude the kind of isolated DNA claims at issue here. 

It is not clear to me that Chakrabarty, Funk Brothers, or 

Prometheus leads inexorably to the conclusion that isolated DNA molecules are not patentable subject matter. I 

decline the invitation to broaden the law of nature exception. 

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 technological problems tendered [by the parties] . . . indicate to us that 

considered action by the Congress is needed.”). 

IV. 

“The rule that the discovery of a law of nature cannot 

be patented rests . . . on the . . . fundamental understanding that they are not the kind of ‘discoveries’ that the 

statute was enacted to protect.” Flook, 437 U.S. at 593. 

Is an isolated kidney patentable? Probably not, but as far 

as I can tell nobody ever thought isolating organs from 

someone’s body was the kind of discovery “that the statute 

was enacted to protect.” In contrast, purifying or isolating 

natural products has historically been exactly the kind of 

discovery protected by the patent statutes. There is a 

century-long history of affirming patent protection for 

isolated and purified biological products ranging from 

hormones to vitamins to proteins to antibiotics. These 

inventions must have seemed miraculous at the time, 

providing previously unknown therapeutic options to 

treat sickness. The fact that these molecules might have 

existed in nature did not foreclose patent protection in 
ASSOCIATION FOR MOLECULAR v. PTO 22

view of the extraordinary benefits accessible to man after 

isolation. 

The Patent Office has, for more than a decade, affirmatively stated its belief that isolated DNA is patentable for the same reasons as isolated vitamins or 

hormones. There is no indication from Congress that this 

view is wrong; to the contrary, it appears Congress also 

believes DNA is patentable. This long-term policy of 

protecting isolated DNA molecules has resulted in an 

explosion of innovation in the biotechnology industry, an 

industry which, unlike the financial services industry or 

even the software industry, depends on patents to survive. Holding isolated DNA not patentable would destroy 

long settled industry expectations for no reason other 

than a gut feeling that DNA is too close to nature to be 

patentable, an arbitrary decision based on a judge-made 

exception. I believe that isolated DNA fragments, which 

have both chemical changes from the naturally occurring 

genomic DNA as well as new utility, are “the kind of 

‘discoveries’ that the statute was enacted to protect.” I 

therefore decline to extend the “laws of nature” exception 

to include isolated DNA sequences. 

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 elements bequeathed to men to use in their work. The 

patents in this case revealed a new molecular understanding about ourselves; “the inventions most benefiting 

mankind are those that ‘push back the frontiers of chemistry, 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 
23 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 entertain” arguments about “the grave risks” generated by 

genetic research.). “The choice we are urged to make is a 

matter of high policy for resolution within the legislative 

process after the kind of investigation, examination, and 

study that legislative bodies can provide and courts 

cannot.” Id. at 317. 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 will not strip an entire 

industry of the property rights it has invested in, earned, 

and owned for decades unchallenged under the facts of 

this case. 
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 

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, 
ASSOCIATION FOR MOLECULAR v. PTO 2

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 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 the court’s 

decision, if sustained, 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 human gene. From a common-sense point of view, most 

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 
3 ASSOCIATION FOR MOLECULAR v. PTO

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 material 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 researchers led by Dr. Mary-Claire King. See Jeff M. Hall et al., 

Linkage of Early-Onset Familial Breast Cancer to Chromosome 17q21, 250 Science 1684 (1990). And Myriad did 

not invent a new method of nucleotide sequencing. Instead, it applied known sequencing techniques to identify 

the nucleotide order of the BRCA genes.1 Myriad’s discovery 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. 

Of course, Myriad is free to patent applications of its 

discovery. As the first party with knowledge of the sequences, 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 

 1 There is some dispute over whether other inventors 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

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 

DNA 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 

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 
5 ASSOCIATION FOR MOLECULAR v. PTO

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 “manifestations 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 distinctive name, character [and] use.’” 447 U.S. at 309-10, 

quoting 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 bacterial strains did not exert an inhibitive effect on one another. 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 Chakrabarty’s invention to be patentable. Chakrabarty, 447 

U.S. at 310. 
ASSOCIATION FOR MOLECULAR v. PTO 6

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 materially 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 minerals, 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 

those alterations that are attendant to their extraction 

does not give the extractor the right to patent the products themselves. 
7 ASSOCIATION FOR MOLECULAR v. PTO

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 

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 

 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 patentability purposes, and I see little support for such a 

distinction in the governing precedents. 
ASSOCIATION FOR MOLECULAR v. PTO 8

(1931) (cleaning a shell by acid and then grinding off a 

layer with an emery wheel did not convert it into a different product). Nor should it make a difference for purposes 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. 

If the changes in the DNA molecule that occur as part 

of the process of isolation render the gene claims patentable, the same analysis would seem to apply to chemical elements that do not appear in their atomic form in 

nature. For example, 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 compound, 

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 it seems plain that elemental 

lithium (like other elements) would not be patentable 

subject matter, even if it could only be extracted from 

nature through an isolation process. 

The principles underlying that analysis apply to genetic 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 remains the same whether the gene is in the body or isolated. 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 genetics, which provides the language of the 

claims, than to chemistry. Aside from Myriad’s cDNA 

claims, its composition claims are not defined by any 
9 ASSOCIATION FOR MOLECULAR v. PTO

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 molecular 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 numerous 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 chemically described. Yet 

those molecules would share only one unifying characteristic: each would code for the same protein as the naturally occurring BRCA1 gene. 

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. It is true that the claimed molecules have been cleaved and that they possess terminal 

groups that differ from those found on naturally occurring 

genes. The majority attaches significance to those facts. 

But the function of the isolated DNA molecules is attributable not to the nature of the isolation process or to the 

identity of the terminal groups on the molecules; the 
ASSOCIATION FOR MOLECULAR v. PTO 10

function of the claimed molecules is dictated by the nucleotide sequence of the gene—a sequence that is determined by nature and that appears in nature exactly as it 

appears in the claimed isolated DNA. 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 starting 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.

Another example underscores the problem with characterizing the isolated gene as a patentable invention. A 

human kidney is a product of nature; it does not become a 

patentable invention when it is removed from the body, 

even if the patentee has developed an improved procedure 

for extracting the kidney, and even if the improved procedure results in some physical or chemical changes to the 
11 ASSOCIATION FOR MOLECULAR v. PTO

kidney at the points where the kidney was attached to the 

host body. But if that is so, then why should an isolated 

gene be treated differently for purposes of section 101? 

While the isolation of a gene involves the alteration of a 

single molecule, it is difficult to accept that it should 

make a difference, for purposes of patentability, whether 

the isolated substance is part of a single molecule, as in 

the case of the BRCA genes, or part of a very large aggregation of molecules, as in the case of a kidney. 

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 

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 something that can be characterized as “isolated” or “extracted” from its natural setting always remains a natural 

product and is not patentable. One could say, for example, 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 manufacture, not a naturally occurring product. In that setting, man has defined the parts that are to be retained 

and the parts that are to be discarded, and he has molded 
ASSOCIATION FOR MOLECULAR v. PTO 12

the retained portion into a product that bears little resemblance to that which occurs naturally. 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 possessed 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 

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 substance 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 ultramarine, but recognizing that if a claimed article is “of such 

 4 By analogy, extracting a slab of marble from the 

earth does not give rise to protectable intellectual property 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

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 vanadium); 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 purpose 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 Mathieson 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 

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; 

that material is the same, structurally and functionally, 

in both the native gene and the isolated form of the gene. 

The structural differences between the claimed “isolated” genes and the corresponding portion of the native 

genes are irrelevant to the claim limitations, to the functioning 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 
ASSOCIATION FOR MOLECULAR v. PTO 14

human body. Indeed, that identity of function in the 

isolated gene is the key to its value. The naturally occurring genetic material 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. 

The Supreme Court’s recent decision in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 132 

S. Ct. 1289, 1293 (2012), does not decide this case, but the 

Court’s analysis is nonetheless instructive. In Mayo, 

which involved method claims, the representative claim 

involved the steps of administering a drug to a subject, 

determining a metabolite concentration in the subject’s 

blood, and inferring the need for a change in dosage based 

on that metabolite concentration. Id. at 1295. The Court 

found that the method was not directed to patent-eligible 

subject matter because it contributed nothing “inventive” 

to the law of nature that lay at the heart of the claimed 

invention, i.e., “the relationships between the concentration in the blood of certain thiopurine metabolites and the 

likelihood that the drug dosage will be ineffective or 

induce harmful side-effects.” Id. at 1294. The Court 

examined “whether the claims do significantly more than 

simply describe these natural relations” and whether the 

“claims add enough to their statements of the correlations 

to allow the processes they described to qualify as patenteligible processes that apply natural laws.” Id. at 1297 

(emphasis in original). In concluding that the claims did 

not add “enough” to the natural laws, the Court was 

particularly persuaded by the fact that “the steps of the 

claimed processes . . . involve well-understood, routine, 

conventional activity previously engaged in by researchers in the field.” Id. at 1294. 
15 ASSOCIATION FOR MOLECULAR v. PTO

Just as a patent involving a law of nature must have 

an “inventive concept” that does “significantly more than 

simply describe . . . natural relations,” Mayo, 132 S. Ct. at 

1294, 1297, a patent involving a product of nature should 

have an inventive concept that involves more than merely 

incidental changes to the naturally occurring product. In 

cases such as this one, in which the applicant claims a 

composition of matter that is nearly identical to a product 

of nature, it is appropriate to ask whether the applicant 

has done “enough” to distinguish his alleged invention 

from the similar product of nature. Has the applicant 

made an “inventive” contribution to the product of nature? Does the claimed composition involve more than 

“well-understood, routine, conventional” elements? Here, 

the answer to those questions is no. 

Neither isolation of the naturally occurring material 

nor the resulting breaking of covalent bonds makes the 

claimed molecules patentable. We have previously stated 

that “isolation of interesting compounds is a mainstay of 

the chemist’s art,” and that “[i]f it is known how to perform such an isolation doing so ‘is likely the product not of 

innovation but of ordinary skill and common sense.’” 

Aventis Pharma Deutschland GmbH v. Lupin, Ltd., 499 

F.3d 1293, 1302 (Fed. Cir. 2007), quoting KSR Int’l Co. v. 

Teleflex, Inc., 550 U.S. 398, 421 (2007). Similarly, the 

structural changes ancillary to the isolation of the gene do 

not render these claims patentable. The cleaving of 

covalent bonds incident to isolation is itself not inventive, 

and the fact that the cleaved molecules have terminal 

groups that differ from the naturally occurring nucleotide 

sequences does nothing to add any inventive character to 

the claimed molecules. The functional portion of the 

composition—the nucleotide sequence—remains identical 

to that of the naturally occurring gene. 
ASSOCIATION FOR MOLECULAR v. PTO 16

The majority suggests that I have “focus[ed] not on 

the differences between isolated and native DNAs, but on 

one similarity: their informational content.” In light of 

Mayo, that approach seems appropriate. The informational content of the nucleotide sequences is the critical 

aspect of these molecules; the terminal groups added to 

the molecules when the covalent bonds are broken—to 

which the majority and concurring opinions attribute 

such significance—are not even mentioned in the claims. 

The nucleotide sequences of the claimed molecules are the 

same as the nucleotide sequences found in naturally 

occurring human genes. In my view, that structural 

similarity dwarfs the significance of the structural differences between isolated DNA and naturally occurring 

DNA, especially where the structural differences are 

merely ancillary to the breaking of covalent bonds, a 

process that is itself not inventive. 

II 

As noted, in addition to the BRCA gene claims discussed 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 laboratory.5 The end product is a human-made invention with 

 5 The appellees argue that the BRCA1 cDNA can be 

isolated from nature, and they refer to a BRCA1 pseudogene called BRCA1P1 that is found in the human 

genome. However, the appellees have failed to demonstrate that the pseudogene consists of the same sequence 

as the BRCA1 cDNA. 
17 ASSOCIATION FOR MOLECULAR v. PTO

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 sequence 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 

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 is not 

entitled to such broad protection. See Mayo, 132 S. Ct. at 

1301, 1303 (examining “how much future innovation is 

foreclosed relative to the contribution of the inventor” and 

warning of the “danger” that overly broad patent claims 

might “foreclose[] more future invention than the underlying discovery could reasonably justify"). 

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 functionality. A claim to tagged segments would not encompass the BRCA1 exons. As to primer functionality, many 
ASSOCIATION FOR MOLECULAR v. PTO 18

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 utility.” 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. 

The other claim to a short segment of DNA, 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 numerous 

molecular variations, but also any sub-sequence of those 

molecules, including portions that fall in the undefined 

range of those molecules denoted “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 
19 ASSOCIATION FOR MOLECULAR v. PTO

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 developing 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 

thicket are “quite real in the calculations of productdeveloping firms”). 

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 constitute patent-eligible subject matter. I think the PTO’s 

practice and guidelines are not entitled to significant 

weight, for several reasons. 
ASSOCIATION FOR MOLECULAR v. PTO 20

First, as we have recognized, the PTO lacks substantive rulemaking authority as to issues such as patentability. Animal Legal Def. Fund v. Quigg, 932 F.2d 920, 930 

(Fed. Cir. 1991). In areas of patent scope, we owe deference only commensurate with “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. 

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 has twice 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 patenteligible. Although the PTO did not “sign” the brief on 

either occasion 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 conclude that the Executive Branch 

has modified its position from the one taken by the PTO 

in its 2001 guidelines and, informally, before that. 

Finally, prior to the Supreme Court’s decision in 

Chakrabarty, the PTO had determined that microorgan-
21 ASSOCIATION FOR MOLECULAR v. PTO

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 the government’s brief in that case) 

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 analysis 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 authority that Congress has not 

accorded it.6 There is no collective right of adverse possession to intellectual property, and we should not create 

one. 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 community were based on longstanding Supreme Court precedent.