Making the Case Against - Specialized Research AI at MIT

Making the Case Against
Gene Patents

Tania Simoncelli1

Sandra S. Park2

On June 13, 2013, the Supreme Court issued a unanimous decision in
Association for Molecular Pathology v. Myriad Genetics, holding that
a naturally occurring DNA segment that has merely been “isolated” is not patent
eligible, and effectively overturning a longstanding policy that had allowed for
patents to be issued on thousands of human genes. Drawing largely on the expert
testimony and arguments presented during the court proceedings, this paper provides
an overview of the discovery and patenting of the BRCA1 and BRCA2 genes at
issue in the case, the impacts of gene patents on biomedical research and innovation
and clinical practice, and the legal analysis presented by the plaintiffs throughout
the case for how patents issued on genes violate the Patent Act and the U.S.
Constitution. Finally, it discusses how the Court’s decision in this case marked
an extraordinary victory not only for the plaintiffs directly involved, but more
generally for women, patients, researchers, civil liberties, and the future of medicine.

1. Making the Case Against Gene Patents
On June 13, 2013, the Supreme Court issued a unanimous decision in Asso-
ciation for Molecular Pathology v. Myriad Genetics, holding that human genes

1. Tania Simoncelli currently serves as Assistant Director for Forensic Science in the
White House Ofﬁce of Science and Technology Policy. She previously served as Science
Advisor to the ACLU and is a coauthor with Sheldon Krimsky of Genetic Justice: DNA Data
Banks, Criminal Investigations and Civil Liberties. The opinions expressed herein are those of the
authors alone and do not necessarily represent the views of the United States Government.
2. Sandra S. Park is a senior attorney at the American Civil Liberties Union Women’s
Rights Project and served as a lead counsel to plaintiffs challenging the patents in Associ-
ation for Molecular Pathology v. Myriad Genetics litigation. The authors thank Myles Jackson
for the invitation to participate in the 2011 Francis Bacon conference, and Katie Clemente,
Michael Chang-Frieden, and Ramya Sekaran for their research assistance.

Perspectives on Science 2015, vol. 23, no. 1
No rights reserved. This work was authored as part of the Contributorʼs ofﬁcial duties as an Employee of
the United States Government and is therefore a work of the United States Government. In accordance
with 17 U.S.C. 105, no copyright protection is available for such works under U.S. law.

doi:10.1162/POSC_a_00161

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Perspectives on Science

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cannot be patented. Finding that “a naturally occurring DNA segment is a
product of nature and not patent eligible merely because it has been isolated,”
the Court put an end to the U.S. Patent and Trademark Ofﬁce’s (USPTO)
fundamentally misguided and longstanding gene patenting policy that had
allowed for thousands of patents to be issued on naturally occurring “isolated”
DNA sequences.

The Court’s decision in the case (hereinafter, AMP) marked an extra-
ordinary victory not only for the twenty plaintiffs directly involved, but
more generally for women, patients, researchers, civil liberties, and the future
of medicine. At issue in the case were patents that had been granted on two
genes (BRCA1 and BRCA2) that have been associated with hereditary forms
of breast and ovarian cancer. Myriad Genetics, a private corporation based
in Utah, had successfully applied for and obtained a suite of patents on these
genes which provided the company with exclusive rights over, and an effec-
tive monopoly on, clinical diagnostic testing or any other use or application
of the genes.

When AMP was initially ﬁled in federal court in 2009, few predicted a
victory for the plaintiffs. The USPTO had been issuing patents on genes for
more than twenty years, the biotechnology industry had grown up around
this practice, and the patent bar viewed gene patenting as status quo. Many
factors contributed to the twists and turns in this case and its ultimate out-
come. Key to its success was the involvement of a diverse and highly com-
mitted group of plaintiffs, experts, and supporters brought together by the
American Civil Liberties Union (ACLU) and the core legal and policy issues
at stake that united them. The community’s success in integrating legal
precedent governing patent eligibility with the implications of gene patents
for public health and biomedicine resulted in a compelling set of arguments
that ultimately prevailed despite what appeared to many interested onlookers
at the offset to be insurmountable challenges.

Drawing largely on the expert testimony and arguments presented during
the court proceedings, this article provides an overview of the core policy and
legal arguments against the patenting of isolated DNA that were at stake in
AMP. First, it presents a brief history and description of gene patenting, the
discovery and patenting of the BRCA1 and BRCA2 genes, and the speciﬁc
patent claims that were challenged in the litigation. Next, it provides a
detailed overview of the detrimental impacts that gene patents have had
on science and innovation. It then outlines the legal analysis articulated by
the plaintiffs throughout AMP for how patents issued on genes violate the
Patent Act and the U.S. Constitution. Finally, it traces the court rulings in the
case and discusses the implications of the Supreme Court’s decision, includ-
ing how the invalidation of these patent claims will serve to beneﬁt patients,
biomedical research and precision medicine.

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The Case Against Gene Patents

The Patenting of Human Genes

2.
The ﬁrst gene patent (Patent No. 4,363,877) was issued to the University of
California in 1982 related to a gene for human chorionic somatotropin, a
growth hormone that promotes breast development during pregnancy (Huang
and Murray 2009). Throughout the 1980’s, scientists continued to obtain
patents on genes whose function they had identiﬁed (Williams-Jones 2002,
pp. 125–6). By the 1990’s, the scope of patent applications had widened, as
applicants sought patents on gene segments whose utility was unknown. For
example, the National Institutes of Health (NIH) announced in 1991 its
applications on 350 gene segments discovered during the Human Genome
Project. NIH stated that its applications were intended to protect the govern-
ment’s rights and to prevent preemptive patenting. Ultimately, however, these
patents were rejected by the Patent Ofﬁce (Schmidt 2000). In October 1992,
the Secretary of the U.S. Department of Health and Human Services reversed
the NIH policy of seeking patents. The trend to seek patents on gene se-
quences, however, was by then ﬁrmly established. In October 1996 the USPTO
announced that it had a backlog of patents covering over 500,000 gene
sequences (Abate 2000, p. A8).

2.1. The USPTO’s Justiﬁcation
The USPTO grants patents pursuant to the Patent Act, enacted by Congress
and codiﬁed at title 35 of the U.S. Code. The Patent Act lays out a number of
criteria for patents, including standards for novelty, utility, non-obviousness,
written description, and subject matter eligibility. Section 101 of the Patent
Act sets forth the basic deﬁnition of “inventions patentable” and states: “Who-
ever invents or discovers any new and useful process, machine, manufacture, or
composition of matter, or any new and useful improvement thereof, may obtain
a patent therefore, subject to the conditions and requirements of the title.”

In 1999 and 2000, the USPTO undertook a process of revising its ex-
amination guidelines for determining whether patent applications met the
“utility” requirement—a criterion that is separate from the subject matter
eligibility analysis under Section 101 (USPTO [1999] 2000). This revision
was sparked by a widespread concern that patents were being issued on very
small segments of genetic material where the utility was unknown. While
the USPTO directed its inquiry to the utility question, several commenters
took issue with the more fundamental question of whether human genes
should be patent eligible subject matter at all under Section 101. For ex-
ample, members of the National Advisory Council for Human Genome
Research of the NIH argued that allowing patents on genes, including util-
ities not demonstrated in the patent, would stiﬂe scientiﬁc discovery and
commercial application (National Advisory Council for Human Genome
Research 2000). The National Breast Cancer Coalition wrote that “scientists

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Perspectives on Science

109

should have free access to the raw fundamental data on the human genome,”
because such “unencumbered access would beneﬁt the public by providing
the greatest opportunity for scientiﬁc advancements against diseases” (Nat’l
Breast Cancer Coalition 2000, p. 77). Others opposed gene patents on the
basis that genes are discoveries rather than inventions and therefore not eligi-
ble for patent protection, or that genes are a fundamental aspect of humanity
(American College of Medical Genetics 2000; Association for Molecular
Pathology 2000; Scherer 2000). Some suggested that the scope of DNA
patent claims be limited to speciﬁc uses and not include claims over the
DNA itself. Still others suggested that the USPTO should seek guidance from
Congress on the matter.

Despite signiﬁcant opposition to DNA patenting, the USPTO solidiﬁed its
policy to issue gene patents through the publication of its revised utility
examination guidelines in 2001, stating that an “isolated and puriﬁed DNA
molecule that has the same sequence as a naturally occurring gene,” including
a gene excised from a natural chromosome, is patentable subject matter
(USPTO 2001, p. 1092). The USPTO’s justiﬁcation? “[A]n excised gene is
eligible for a patent as a composition of matter or as an article of manufacture
because that DNA molecule does not occur in that isolated form in nature”
(USPTO 2001, p. 1093). The USPTO saw no reason to distinguish genes
from other chemicals and further argued that when chemicals (including
DNA) are patented, “progress is promoted because the original inventor has
the possibility to recoup research costs, because others are motivated to invent
around the original patent, and because a new chemical is made available as a
basis for future research” (USPTO 2001, pp. 1094–5). The USPTO did require
that at least “one speciﬁc, substantial, and credible utility” be demonstrated
before a DNA molecule could be patented, thus responding to concerns that
small DNA fragments, including expressed sequence tags (ESTs),3 were being
patented where the utility had not yet been ascertained or substantiated.

Thus, by 2001, the USPTO had established in no uncertain terms that
it would grant patents on segments of naturally occurring DNA that had
simply been isolated from a human cell so long as one utility—such as a
correlation with a disease—had been established. In 2005, scholars estimated
that this policy had resulted in explicit claims over 4,382 of the 23,688
protein-coding human genes—18.5% of human genes ( Jensen 2005).
These claims were contained in 4270 patents owned by 1156 different as-
signees, with roughly 63% assigned to private ﬁrms (Jensen 2005). At least
3000 of the patented genes were controlled by a single entity, while the
remaining genes involved multiple assignees.

3. Expressed sequence tags are small stretches of DNA within a coding region of a gene.

They can be used to identify full-length genes as well as for gene mapping.

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110

The Case Against Gene Patents

2.2. BRCA1 and BRCA2 Patents
In the 1930s and 1940s, scientists began documenting unusually high
rates of breast cancer in certain families, leading them to suspect that cancer
susceptibility may be hereditary (Davies and White 1995, p. 81). However,
it was not until decades later that scientists had acquired sufﬁcient tools and
knowledge about the human genome to allow them to begin to systemati-
cally search for a gene or genes that might be linked to this hereditary risk
(Davies 1995, p. 88). By the late 1980’s, researchers around the world were
looking for the genetic basis of breast and ovarian cancer (Williams-Jones
2002, p. 131). In 1990, a team led by Mary-Claire King announced that
they had identiﬁed the long arm of chromosome 17 as the site of a gene
associated with increased risk for breast cancer, dubbed BRCA1. In August
1994, Mark Skolnick and researchers at Myriad Genetics, University of Utah,
NIH, and McGill University sequenced that gene. Skolnick’s research was
backed by $5 million in federal funding, as well as funding from Eli Lilly (Williams-Jones 2002, p. 131). Myriad ﬁrst ﬁled patents on BRCA1 in the U.S. in 1995, and by 1998, patents with broad claims over the gene itself had been issued. NIH ﬁled a competing application, which it ultimately withdrew after two of its researchers were named on the Myriad patent. OncorMed, another com- pany doing research on BRCA1, did obtain a competing patent (Patent No. 5,654,155; Murray 1999) for a non-mutated BRCA1 allele describ- ing a DNA sequence more likely to be found in the population than the wildtype sequence described in the Myriad patent. Myriad and OncorMed subsequently ﬁled suit against each other, cases that were set- tled when Myriad acquired OncorMed’s patents (Williams-Jones 2002, pp. 132–3). Myriad ﬁrst ﬁled applications relating to BRCA2 in 1996, which were approved in 1998. These patents were accompanied by additional controversy, because Myriad’s application had been ﬁled the day before the BRCA2 sequence was to be published in Nature by the UK consor- tium led by Michael Stratton at the Institute for Cancer Research and the Sanger Centre (Williams-Jones 2002, p. 133). Although both the Myriad Genetics and Stratton groups claimed priority in isolating the BRCA2 gene, a citation network analysis demonstrated that the scientiﬁc community tends to believe that the Stratton group was ﬁrst to map and sequence it.4 4. Declaration of Shobita Parthasarathy. 2009, ¶¶12–13. Ass’n for Molecular Pathology v. U.S. Patent and Trademark Ofﬁce, 702 F.Supp. 2d 181 (2009). l D o w n o a d e d f r o m h t t p : / / d i r e c t . m i t . / e d u p o s c / a r t i c e – p d l f / / / / 2 3 1 1 0 6 1 7 8 9 9 7 4 p o s c _ a _ 0 0 1 6 1 p d . / f b y g u e s t t o n 0 7 S e p e m b e r 2 0 2 3 Perspectives on Science 111 3. What Was Patented? The term “gene patent” has been used to refer to a wide range of different patent claims. A single gene can have multiple patents. And a single pa- tent can have dozens of claims. The most controversial claims fall in two categories: composition of matter claims to “isolated DNA,” and claims to methods for identifying a sequence or the existence of a mutation. The controversy around gene patenting has centered primarily on composition claims on isolated, but otherwise unaltered, human genomic DNA, because these claims have the effect of covering any and all uses of the isolated DNA molecule. In the Myriad litigation, nine of the challenged claims were composition of matter claims on “isolated” BRCA1 and BRCA2 DNA.5 These claims covered DNA coding for the BRCA1 and BRCA2 proteins, DNA with the wild-type nucleotide sequence, DNA with as few as 15 of the nucleotides of the BRCA1 gene, DNA coding for naturally occurring mutated forms of the BRCA2 protein, and DNA molecules with speciﬁed, naturally occurring mutations. For example, one of the challenged claims to isolated DNA was as follows: “An isolated DNA coding for a BRCA1 polypeptide, said polypeptide having the amino acid sequence set forth in SEQ ID NO. 2” (where SEQ ID NO. 2 lays out the wild-type sequence). Because virtually any use of the gene requires that it be isolated—namely, excised from the cell, as deﬁned by the USPTO and in the patents—the claim has the effect of covering any and all uses of the BRCA1 gene—i.e., DNA coding for a BRCA1 poly- peptide. In addition, many different DNA sequences, or combinations of nucleotides, can code for the same polypeptide. As such, with this claim and others, Myriad has patented not just one version of the BRCA1 gene that it may have initially sequenced, but every possible version of the gene that exists in the US population. Five of the claims challenged in AMP were method claims, where the purported method involves comparing or analyzing two genetic sequences for the purpose of determining whether a mutation exists.6 For example, claim 1 of Patent ‘857 stated: “A method for identifying a mutant BRCA2 nucleotide sequence in a suspected mutant BRCA2 allele which comprises comparing the nucleotide sequence of the suspected mutant BRCA2 allele 5. The claims included: claims 1, 2, 5, 6, and 7 of Patent 5,747,282; claims 1, 6, 7 of Patent 5,837,492; claim 1 of Patent 5,693,473. 6. The claims included: claim 1 of Patent 5,709,999; claim 1 of Patent 5,710,001; claim 1 of Patent 5,753,441; claims 1 and 2 of Patent 6,033,857. There was also a sixth method claim that was challenged, claim 20 of Patent ‘282, involving comparing the rate of growth of a host cell in the presence of a possible cancer therapeutic to the rate of growth of the cell in the absence of the possible cancer therapeutic. l D o w n o a d e d f r o m h t t p : / / d i r e c t . m i t . / e d u p o s c / a r t i c e – p d l f / / / / 2 3 1 1 0 6 1 7 8 9 9 7 4 p o s c _ a _ 0 0 1 6 1 p d . / f b y g u e s t t o n 0 7 S e p e m b e r 2 0 2 3 112 The Case Against Gene Patents with the wild-type BRCA2 nucleotide sequence, wherein a difference be- tween the suspected mutant and the wild-type sequence identiﬁes a mutant BRCA2 nucleotide sequence.” With this claim, Myriad patented any process by which one genetic sequence—such as that of a patient— is compared with the normal, or wild-type sequence. No tools or steps are speciﬁed; a person could violate the claim simply by mentally comparing two given sequences. The Impacts of Gene Patents on Innovation, Clinical Practice, and Patient 4. Care, and Research 4.1. Patents and Progress The Congress shall have the power…To promote the Progress of Science and the useful Arts, by securing for limited Times to Authors and Inventors the exclusive Right to their respective Writings and Discoveries. (United States Constitution, Article I, Section 8, Clause 8) The Constitution made clear that patent protection should serve to fur- ther scientiﬁc advancement. Also implicit in this clause is the notion that, without patent protection, such progress might not occur. Individuals might not want to disclose or pursue such inventions, for example, be- cause of concerns that others might copy their ideas and reap the beneﬁts (the so-called free rider problem). By rewarding an inventor with an ex- clusive right to market or use his or her innovation for a period of time (e.g., 20 years), the patent system helps stimulate innovation by providing inventors and their investors with the assurance that they will beneﬁt from their invention. While it may be true that the patent system serves to foster progress overall, it is not the case that strong patent protection in a given arena necessarily stimulates innovation. Joseph E. Stiglitz, Nobel Prize-winning economist and former Chief Economist of the World Bank, explains that there are two fundamental inefﬁciencies with the patent system that can work to impede innovation. First, the system of rewarding an inventor with an exclusive right to use his or her innovation results in restricting the use of knowledge.7 There are always social costs associated with this restric- tion, since knowledge is a “public good”— one that is non-excludable and non-rivalrous in consumption (everyone potentially can beneﬁt from it, and there is no extra cost associated with an additional person gaining those beneﬁts). Second, the patent system grants temporary monopoly power, 7. Declaration of Joseph E. Stiglitz. 2009, ¶11, Ass’n for Molecular Pathology v. U.S. Patent and Trademark Ofﬁce, 702 F. Supp. 2d 181 (2009). l D o w n o a d e d f r o m h t t p : / / d i r e c t . m i t . / e d u p o s c / a r t i c e – p d l f / / / / 2 3 1 1 0 6 1 7 8 9 9 7 4 p o s c _ a _ 0 0 1 6 1 p d . / f b y g u e s t t o n 0 7 S e p e m b e r 2 0 2 3 Perspectives on Science 113 which can lead to inequities as well as major distortions of resource allocations.8 The social costs of these distortions and inefﬁciencies can outweigh the bene- ﬁts of disclosure, especially in cases where patents granted are overly broad or improperly awarded on basic knowledge or natural laws or phenomena. Gene patenting is a classic—if not extreme—example where social costs clearly outweigh beneﬁts. First, the problem of restricting knowledge is especially pronounced when patents are issued on isolated DNA. Sir John Sulston, a Nobel Prize winning scientist who played a central role in the human genome project, describes genes as “the most fundamental information about humanity.”9 Our DNA embodies a linear genetic code consisting of four nucleic acids – adenine (A), thymine (T), cytosine (C), and guanine (G)—that gets copied more or less faithfully from one generation to the next.10 The ordering of this sequence encodes for the generation of our proteins and the development and functioning of our cells. Because DNA, unlike other chemicals, is ﬁrst and foremost an informational molecule, patents on DNA are essentially patents on information. This is true regardless of whether the DNA is in a so-called “isolated” state or not. As Sulston explains, “‘Isolating and purifying’ a gene is simply copying it into another format. It’s like taking a hardback book written by someone else, publishing it in paper- back and then claiming authorship because the binding is different.”11 The social costs of granting monopoly power on genes are also high. A gene patent holder is given exclusive rights over all uses of that gene. This may include preventing individuals from having their gene tested (regard- less of method), preventing scientists from developing diagnostic tests or therapeutics involving that gene, controlling access to information about that gene, eliminating all competition for any commercial applications, and laying claims to future discoveries that others make about that gene, such as the ﬁnding of additional disease-relevant mutations. At the same time, the public gets little, if anything, in return for the granting of a patent on a gene. The disclosure of information—in this case, the publishing of the sequence of the gene—is something that occurs frequently in the public domain and that likely would occur in short order regardless of whatever incentive is provided by the patent.12 There 8. Declaration of Joseph E. Stiglitz. 2009, ¶11, Ass’n for Molecular Pathology v. U.S. Patent and Trademark Ofﬁce, 702 F. Supp. 2d 181 (2009). 9. Declaration of John E. Sulston. 2009, ¶10, Ass’n for Molecular Pathology v. U.S. Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009). 10. Declaration of Joseph E. Stiglitz. 2009, ¶13, Ass’n for Molecular Pathology v. U.S. Patent and Trademark Ofﬁce, 702 F. Supp. 2d 181 (2009). 11. Declaration of John E. Sulston. 2009, ¶26, Ass’n for Molecular Pathology v. U.S. Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009). 12. Declaration of Fiona E. Murray. 2010, ¶¶7–20, Ass’n for Molecular Pathology v. U.S. Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2010). l D o w n o a d e d f r o m h t t p : / / d i r e c t . m i t . / e d u p o s c / a r t i c e – p d l f / / / / 2 3 1 1 0 6 1 7 8 9 9 7 4 p o s c _ a _ 0 0 1 6 1 p d . / f b y g u e s t t o n 0 7 S e p e m b e r 2 0 2 3 114 The Case Against Gene Patents is in fact considerable evidence that patent protection is not necessary for encouraging gene discoveries or the advent of genetic tests, and in fact, may even serve to stiﬂe data sharing, research and development in bio- medicine. As described below, gene patents have served to undermine clinical diagnostic testing and patient care and impede research and data sharing. 4.2. Impacts of Gene Patents on Clinical Diagnostic Testing The Committee…found no cases in which possession of exclusive rights was necessary for the development of a genetic test…Furthermore, exclusive rights do not result in faster test development…The Committee [also] found that patents on genes and associations threaten the development of new and promising testing technologies. (Secretary’s Advisory Committee on Genetics, Health and Society, April 2010) Gene patent proponents argue that patent protection is necessary to ensure the development of molecular diagnostic tests. However, most of the new clinical DNA tests that have been developed each year have not concerned patented genes. Moreover, genetic tests were on the market for BRCA-related breast cancer, as well as hearing loss, Spino- cerebellar ataxia (SCA), Long QT Syndrome, Canavan disease, and hemo- chromatosis before patents were awarded and the relevant patent holder started to offer testing.13 Rather than allowing broad availability of testing, patent holders in these instances used their exclusive rights to shut down or prevent clinical laboratories from offering testing. Several laboratories in the United States were offering BRCA testing at the time that Myriad was awarded its patents. One by one, Myriad worked to shut down testing at each of these sites. OncorMed, a medium-sized start-up biotechnology company, had been highly involved in BRCA gene discovery research, and developed its testing services based on its own patents and licenses related to the BRCA genes. In 1998, after a series 13. In the case of hemochromatosis, a survey found that, while awareness of the patent appeared to inhibit the adoption by clinical laboratories, patents were not necessary for rapid introduction of the test (Declaration of Mildred Cho. 2009, ¶¶20–21, Ass’n for Molecular Pathology v. U.S. Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009)). Laboratories began immediately offering clinical genetic tests for hemochromatosis after the discovery of the gene in August 1996. The mean time from publication to adoption was 14 months, and 60% reported introducing the test before the ﬁrst patent was issued in January 1998 (Decla- ration of Mildred Cho. 2009, ¶21, Ass’n for Molecular Pathology v. U.S. Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009)). l D o w n o a d e d f r o m h t t p : / / d i r e c t . m i t . / e d u p o s c / a r t i c e – p d l f / / / / 2 3 1 1 0 6 1 7 8 9 9 7 4 p o s c _ a _ 0 0 1 6 1 p d . / f b y g u e s t t o n 0 7 S e p e m b e r 2 0 2 3 Perspectives on Science 115 of lawsuits that settled out of court, Myriad bought OncorMed’s patents and testing services for an undisclosed sum.14 Arupa Ganguly, a professor in the Department of Genetics at the Hos- pital of the University of Pennsylvania and the Director of the University of Pennsylvania Genetic Diagnostic Laboratory (GDL) offered comprehen- sive screening of the BRCA1 and BRCA2 genes for both research and clin- ical purposes. Starting in May 1998, Dr. Ganguly, her colleague Dr. Haig Kazazian, and the University of Pennsylvania general counsel received a series of letters from Myriad Genetics and their lawyers that asserted that Myriad’s BRCA patents covered, among other things, “composition of mat- ter covering the BRCA1 gene [and] any fragments of the BRCA1 gene” and “the BRCA1 gene sequence, mutations in the BRCA1 gene, […] and methods for detecting alterations in the BRCA1 sequence.” The letters stated that their testing activities were infringing their patents and de- manded that they “cease all infringing activity.”15 Dr. Ganguly had also been providing BRCA testing at relatively low cost for a research project sponsored by the National Cancer Institute (NCI) that involved 8 cancer centers across the United States. Myriad sent a letter to NCI that made clear that a license was required for any third-party laboratory to offer such testing. Georgetown University, one of the 8 centers participating in the study, received a letter from Myriad in 1999, demanding that Georgetown no longer send genetic samples, because such activity, in their opinion, infringed Myriad’s BRCA patents. As a result of these letters, Dr. Ganguly felt she had no choice but to cease all BRCA1 and BRCA2 testing, whether for research or clinical purposes, and to entirely abandon this area of research. Cease and desist letters were sent by Myriad to other laboratories and university researchers. A survey of U.S. laboratory directors conducted in 2003 revealed that nine labs reported that they had stopped performing tests for BRCA1 and BRCA2 (Cho et al. 2003). Dr. Harry Ostrer, who was then Director of both the Human Genetics Program and Molecular Genetics Laboratory at the NYU Langone Medical Center, received a letter from Myriad in 1998 stating, “I understand that you are either currently providing diagnostic testing services for BRCA1 or are interested in initi- ating such a service.” The letter made clear that such testing would violate Myriad’s patents on the BRCA genes and offered Dr. Ostrer an extremely limited license to do single mutation tests and mutation panels of up to only 4 mutations for patients of Ashkenazi Jewish descent. Dr. Ostrer l D o w n o a d e d f r o m h t t p : / / d i r e c t . m i t . / e d u p o s c / a r t i c e – p d l f / / / / 2 3 1 1 0 6 1 7 8 9 9 7 4 p o s c _ a _ 0 0 1 6 1 p d . / f b y g u e s t t o n 0 7 S e p e m b e r 2 0 2 3 14. Declaration of Shobita Parthasarathy. 2009, ¶¶22, 24, 27, Ass’n for Molecular Pathology v. U.S. Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009). 15. Declaration of Arupa Ganguly. 2009, ¶¶2–7, Ass’n for Molecular Pathology v. U.S. Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009). 116 The Case Against Gene Patents chose not to enter into the licensing arrangement because it would not have allowed him to do full BRCA1/2 genetic testing. Myriad is not the only patent holder that used its exclusive rights over genes to stop laboratories from offering genetic testing. Similar actions were taken by patent holders in regards to genetic tests associated with hearing loss, Alzheimer’s disease,16 Long QT Syndrome,17 Canavan disease,18 asthma, and Hemochromatosis.19 A scientiﬁc survey of laboratory directors in the United States revealed that 25% had stopped performing a clinical test that they had developed and were offering because of a gene patent or license, and that 53% had decided not to develop or perform a test for clinical or research purposes because of a patent.20 Different labs may utilize different methodologies for performing genetic tests, and interpretation of the results of those tests can be subjective. Where 16. Athena Diagnostics has intermittently used its exclusive rights to various hearing loss and Alzheimer’s disease genes to stop laboratories from offering testing. (Secretary’s Advisory Committee on Genetics, Health, and Society [SACGHS] 2010, p. 21). 17. Patent enforcement with regards to Long QT Syndrome (LQTS) meant that no genetic test was made available at all for some period of time (SACGHS 2010, pp. 3–4). LQTS is a disorder of the heart’s electrical system characterized by irregular heart rhythms that accounts for a small but signiﬁcant fraction of sudden death in young children. The genetics of the disorder are complex: 9 molecular subtypes have been identiﬁed involving mutations along 12 genes. Genetic testing is critical for determining the subtype and, respectively, the most appropriate therapy for the disorder. For example, beta blockers are effective therapy for some subtypes, but can actually trigger arrhythmias in patients with other subtypes. DNA Sciences held an exclusive license for genetic testing for several genes associated with LQTS, but rather than developing a test, the company used patent enforcement to prevent another company, GeneDX, from offering a test. As a result, no testing for LQTS was offered for a 2-year period. At least one patient died during this time at the age of 10 because her LQTS went undiagnosed. 18. Miami Children’s Hospital enforced its patent on the Canavan disease gene, resulting in laboratories stopping testing or paying a royalty fee to continue performing testing (SACGHS 2010, H-6). 19. A study of the impacts of patenting and licensing on genetic testing for hemochroma- tosis, a common condition affecting 1 in 200 to 1 in 300 people of Northern European descent and with a carrier frequency of up to 1 in 10, found that 26% of labs had not developed and were not performing the test, and 4% had stopped performing the test, with 30 out of 36 of those labs citing patents as a reason (SACGHS 2010, E-12-E-13). 20. Declaration of Mildred Cho. 2009, ¶¶11–15, Ass’n for Molecular Pathology v. U.S. Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009). Gene patents may have especially discourag- ing effects on the development of genetic tests for rare hereditary disorders. As the President of Gene Dx explains, a company focused on the development of genetic tests for rare hereditary disorders. The company president explained, “[G]ene patents have a severe negative impact on the development, and thus the availability, of genetic testing for rare disorders [… ] I can assure the committee that any gene on which there is patent protection falls to the very bottom of my quite extensive list of genetic tests in which my company is interested” (SACGHS 2010, p. 30). l D o w n o a d e d f r o m h t t p : / / d i r e c t . m i t . / e d u p o s c / a r t i c e – p d l f / / / / 2 3 1 1 0 6 1 7 8 9 9 7 4 p o s c _ a _ 0 0 1 6 1 p d . / f b y g u e s t t o n 0 7 S e p e m b e r 2 0 2 3 Perspectives on Science 117 only one lab runs a genetic test, that lab may be less likely to identify errors in its testing method or analysis. Proﬁciency testing and sample exchange pro- grams are other aspects of quality control that are jeopardized.21 Moreover, where a test is developed by a single patent holder, a lack of competition means that there is little incentive for that entity to invest in updating a genetic test or ensuring its accuracy or that it reﬂects the best available science. Myriad’s monopoly on BRCA testing in the United States allowed it to dictate how these genes should be tested and whether and how new infor- mation should be incorporated into its testing system. In 2001, researchers at the Institut Curie in France announced that they had found large cancer- causing rearrangements in the BRCA1 gene that were not included as part of Myriad’s test offerings. Myriad initially refused to acknowledge that its test was incomplete. At least one lab inquired with Myriad as to whether they could perform testing for these large rearrangements, but Myriad refused.22 A 2006 study found that approximately 12% of women from high risk families with breast cancer had likely received false negative test results from Myriad as a result of its failure to test for these additional rearrangements (Walsh et al. 2006). It was only after several years and signiﬁcant pressure from the scientiﬁc community that the company added methods to detect these structural mutations. But rather than incorporating the test into its existing system, Myriad chose to market the test as a separate test (“BRCA Analysis Rearrangement Testing” or BART), at an additional cost of $700
for most patients. Myriad maintained this separate testing regime even after
the National Comprehensive Cancer Network issued guidelines recom-
mending that all patients who are advised to obtain genetic testing, and
who are not yet aware of a familial mutation, receive large rearrangement
testing (Nat’l Comprehensive Cancer Network 2012). Several lab directors
have stated that they would reﬂexively conduct large rearrangement test-
ing in cases where a negative result is received through full sequencing.23
Some have also stated they would use newer testing methods (such as micro-
array analysis) that are expected to result in improved testing quality and
efﬁciency.

21. Declaration of David Ledbetter. 2009, ¶23, Ass’n for Molecular Pathology v. U.S.

Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009).

22. Declaration of Ellen Matloff. 2009, ¶¶6–7, Ass’n for Molecular Pathology v. U.S. Patent

and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009).

23. Declaration of David Ledbetter. 2009, ¶¶17–8, Ass’n for Molecular Pathology v. U.S.
Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009); Declaration of Wendy Chung. 2009,
¶18. Ass’n for Molecular Pathology v. U.S. Patent and Trademark Ofﬁce, “Declaration of Wendy
Chung,” 702 F.Supp.2d 181 (2009); Declaration of Harry Ostrer. 2009, ¶9, Ass’n for
Molecular Pathology v. U.S. Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009).

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The Case Against Gene Patents

4.3.

Impacts of Gene Patents on Patient Care

How do I explain to a patient that someone prevents me from looking at and
characterizing a segment of her genome? The patient no longer has the ability
to control her own body and the testing that can be done. How do I explain
that I am not allowed by law to provide a test based on a part of her genome,
a test that both the patient and her physician are asking me to perform,
and that is necessary for diagnosis? (Leonard 2002, p. 1388)

Genetic testing can provide vital information to a patient. Not only might it
inform a patient of her risk for a hereditary disease or condition, but more
and more, genetic testing can be used to determine appropriate preventive
care or treatment options. In the case of BRCA testing, research has shown
that a woman who tests positive for a BRCA mutation can reduce her risk
of cancer through physical activity and avoiding obesity. Some women opt
for prophylactic mastectomy or oophorectomy, major life-altering surgeries
that can dramatically reduce their risk of cancer. For women who have been
diagnosed with cancer, recent studies have shown that certain forms of
chemotherapy may be more effective in targeting BRCA-mutated cells.24
Patients faced with these critical decisions need timely, reliable infor-
mation about their genetic status. Gene patents have interfered with a
patient’s access to testing in a number of ways. First, because these patents
allowed the patent holder to prevent other laboratories from offering testing,
patients were in some cases not able to obtain conﬁrmatory testing from
another laboratory in the event of either a negative or positive test result
(SACGHS 2010, pp. 43–4). Conﬁrmatory testing is an integral part of
patient care. In the case of a breast cancer patient’s care, BRCA testing could
only be performed once and by only one lab in the country, unlike most any
other test, such as examining tumors to determine cancer type and imaging
to determine the spread of cancer.25

Second, testing by only one lab in the country can place artiﬁcial, unnec-
essary limitations on how and when information is shared with patients.
Dr. Wendy Chung, a professor at Columbia University, is co-investigator
of the Breast Cancer Family Registry, a study funded by the National Cancer
Institute that examines genetic and environmental factors inﬂuencing cancer
susceptibility and clinical outcomes in high risk individuals.26 As part of

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24. Declaration of Susan M. Love. 2009, ¶11, Ass’n for Molecular Pathology v. U.S. Patent

and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009).

25. Declaration of Susan M. Love. 2009, ¶¶12–19, Ass’n for Molecular Pathology v. U.S.

Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009).

26. Declaration of Wendy Chung. 2009, ¶¶9–14, Ass’n for Molecular Pathology v. U.S.

Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009).

Perspectives on Science

119

this study, Dr. Chung provides genetic counseling for patients in the study
and her lab performs sequencing of the BRCA genes. Chung feels she has
an ethical responsibility to inform her patients of their BRCA status, but
the patents forbade her from doing so. As a result, for those patients who
opt to learn their BRCA status (approximately 300 per year; a process that
takes 2–3 weeks), Chung was forced to send their samples to Myriad Genetics
for testing, even while her own lab could have provided testing on site within
48 hours. This difference in time can be highly signiﬁcant for a woman
who may be making critical decisions regarding her course of treatment or
care, for example, where she is scheduled to undergo a lumpectomy and
would like to know her BRCA status to determine whether to opt instead
for a full mastectomy.

Third, patents on genes have allowed the cost of genetic testing to be at
the whim of the patent holder or exclusive provider of the test. As of August
2013, Myriad charged $3,340 for its BRACAnalysis test, and an additional $700 for its large rearrangement test (“Myriad raises price of BRCA testing,
again” [Yale 2010]). The cost has proven out of reach for many women who
either did not have insurance, whose insurance did not cover the cost of the
test, or whose insurance had been unable to enter into a contract with Myriad.
Only 130 million of America’s 308 million people are covered for Myriad’s
testing.27 Myriad operates a program to help cover the cost of testing for
some indigent women, but the program only applies to women who have
an income that is lower than $12,000 per year, who have already been diag- nosed with cancer, and who are uninsured.28 While access is an issue for many medical services, it is generally the case that competition drives down costs of services. Moreover, in the speciﬁc case of BRCA testing, several clinical genet- icists stated that, were it not for the threat of patent infringement, they would be in a position to offer testing at a lower rate or on a sliding cost scale.29 Fourth, gene patents may have prevented patients from obtaining a more comprehensive assessment of their genetic risk. For example, several multi- plex testing technologies have been developed that allow for simultaneous 27. Declaration of William E. Rusconi. 2009, ¶4, Ass’n for Molecular Pathology v. U.S. Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009). 28. Declaration of Ellen Matloff. 2009, ¶12. Ass’n for Molecular Pathology v. U.S. Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009). 29. Declaration of Haig H. Kazazian. 2009,¶8, Ass’n for Molecular Pathology v. U.S. Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009); Declaration of Ellen Matloff. 2009, ¶¶12, 14, Ass’n for Molecular Pathology v. U.S. Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009); Declaration of Harry Ostrer. 2009, ¶8, Ass’n for Molecular Pathology v. U.S. Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009); Declaration of Elsa Reich. 2009, ¶¶6, 8, 13. Ass’n for Molecular Pathology v. U.S. Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009). l D o w n o a d e d f r o m h t t p : / / d i r e c t . m i t . / e d u p o s c / a r t i c e – p d l f / / / / 2 3 1 1 0 6 1 7 8 9 9 7 4 p o s c _ a _ 0 0 1 6 1 p d . / f b y g u e s t t o n 0 7 S e p e m b e r 2 0 2 3 120 The Case Against Gene Patents testing of multiple genetic markers with a single test that would be more efﬁcient than conducting a series of individual tests. These multiplex assays are more efﬁcient than traditional testing methods and are essential for investigating complex diseases such as cancer and autism, where multiple genes are thought to play a causative role. However, the thicket of intel- lectual property rights that resulted from patent claims on isolated genes prevented labs from reporting out information that relates to areas of arrays where patented genes lie.30 This means that patients may have re- mained undiagnosed or been presented with an incomplete analysis of their genetic risk for a given condition. A 2010 study by Dr. Mary-Claire King established that testing of 21 genes associated with breast and ovarian cancer could be conducted accurately and efﬁciently, providing a more personalized assessment of cancer risk than is currently offered through Myriad’s testing of only 2 genes ( Walsh et al. 2010). Recently, the Uni- versity of Washington drew on this study to begin offering the BROCA test, which screens 40 genes for hereditary breast and ovarian cancer risk (University of Washington 2013). BRCA1 and BRCA2 were included in this clinical test only after the Supreme Court ruled to invalidate Myriad’s patent claims. Finally, where only one lab performs a genetic test, a single company dictates the standards of patient care for that testing. This includes not only what test is offered and when and under what circumstances it is up- dated to reﬂect new information or improved technology, as discussed above, but also important contextual issues such as the appropriateness of genetic counseling and whether testing will be made available through a physician or directly to the consumer. As Shobita Parthasarathy de- scribes, by shutting down all other major BRCA testing providers in the late 1990s, Myriad came to dictate the standards for patient care in breast cancer genetic testing (Parthasarathy 2007). Other models that existed prior to Myriad’s assertion of its patents that had included more comprehensive care, genetic counseling, and an emphasis on research are no longer available to women and were replaced with a single model for breast cancer genetic testing.31 30. At least two cases have been reported to date where a laboratory, utilizing multiplex testing methods, was forced to mask test results from patients in order to avoid violating a gene patent. (SACGHS 2010, p. 41). See also Sulston Declaration 2009 ¶38, Ass’n for Molecular Pathology v. U.S. Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009); Ledbetter Declaration 2009 ¶24, Ass’n for Molecular Pathology v. U.S. Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009). 31. Declaration of Shobita Parthasarathy. 2009, ¶¶29–31, Ass’n for Molecular Pathology v. U.S. Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009). l D o w n o a d e d f r o m h t t p : / / d i r e c t . m i t . / e d u p o s c / a r t i c e – p d l f / / / / 2 3 1 1 0 6 1 7 8 9 9 7 4 p o s c _ a _ 0 0 1 6 1 p d . / f b y g u e s t t o n 0 7 S e p e m b e r 2 0 2 3 Perspectives on Science 121 4.4. Effects of Gene Patents on Research A strict interpretation of our results suggests that follow-on genetic researchers forego about one in ten research projects […] through the causal negative impact of a gene patent grant. (Huang 2009, 1214) Gene patent proponents have argued that patent protection is necessary for obtaining capital investment for initial gene discovery. However, avail- able evidence shows the opposite: unlike other discoveries such as chemical compounds that have pharmaceutical potential and require lengthy and expensive further development in order to become commercially available, patents on genes do not appear to be necessary to create incentives for initial discoveries or for the development of commercial applications, in- cluding diagnostics. A study of gene patents issued in the United States showed that two-thirds were for discoveries funded by the U.S. government (Schissel et al. 1999). The discovery of the BRCA genes arose out of a context of increasing international scientiﬁc, medical and public interest in breast cancer. The National Institutes of Health (NIH) contributed approximately one-third of the funding toward the discovery of BRCA1, funded a six-person research team to ﬁnd the BRCA genes, and provided approximately $2 million in research grants to the University of Utah for
this research.32 In addition to the government, disease advocacy groups
often contribute to and drive the discovery of genes.33

Staunch defenders of gene patents have also argued that the basic tenet of
the patent system to require disclosure of the invention serves to promote
follow-on research post initial gene discovery.34 However, a rigorous probing
of this question indicated that rather than promoting research, gene pa-
tents have an inhibitory effect on future knowledge production. Speciﬁcally,
the study, conducted by Fiona Murray and Kenneth Huang at MIT, ex-
amined more than 1,000 gene discoveries and found that follow-on genetic
researchers forego approximately one in ten research projects because of

32. Declaration of Shobita Parthasarathy. 2009, ¶18, Ass’n for Molecular Pathology v. U.S.

Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009).

33. As the Executive Director of the Claire Altman Heine Foundation, an organization
focused on the prevention of spinal muscular atrophy (SMA), explains: “In the case of SMA,
the patent holder did not even bear the ﬁnancial burden of the discovery, rather an advocacy
group and patients and families suffering from the disease donated funds and tissue samples
to a researcher who then patented her discovery and sold it” (SACGHS 2010, p. 25).

34. For example, the Biotechnology Industry Organization (BIO) has stated that “the
patent system inherently operates to disseminate rather than sequester knowledge” (BIO
2013, p. 22. Biotechnology Industry Organization. Ass’n for Molecular Pathology v. Myriad
Genetics, Inc. “Brief for Amicus Curiae the Biotechnology Industry Organization in Support
of Respondents,” No. 12-398 (2013)).

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122

The Case Against Gene Patents

the causal impact of gene patents.35 Moreover, this trend was found to be
exacerbated in situations when patents are broad in scope, privately owned, or
where the patented genes are closely linked to human disease, and especially
cancer. In applying these results to the patents held by Myriad, Murray esti-
mated that the patents on BRCA1 and BRCA2 have negatively impacted
the accumulation of public knowledge of these genes by between 5 and 10%.36
Myriad responded to criticism of the effect of gene patents on research by
noting that it does not object to research and that more than 18,000 scientists
have researched the BRCA genes, publishing more than 5,600 research
papers on BRCA1 and over 3,000 research papers on BRCA2. The problem
with this argument is that these numbers refer to research papers that
include any reference to the genes, whether or not sequencing was actually
performed,37 and tell us nothing about how many papers would have been
published had the genes not been patented. Moreover, the patents gave
Myriad the power to deﬁne “research,” thereby allowing it to shut down labs
that did not meet its criteria.38

Surveys have also revealed that many practitioners believe their research
has been negatively impacted by patents on genes. In a survey of clinical
laboratory directors conducted by Mildred Cho et al., 85% of respondents
stated that gene patents have resulted in less sharing of information among
researchers. In the same study, 67% of respondents believed that patents

35. The researchers examined the inﬂuence of gene patenting on the long-run supply of
public knowledge by examining 1279 human gene patent-paper pairs: cases where a gene
discovery is both published in an academic journal and patented. In such cases, there is
typically a three- to four-year lag between the publication of a paper on a gene sequence
and the issuance of a patent disclosing the sequence of that gene. During that lag period,
the not-yet patented information is essentially part of the public knowledge stream. Once a
patent is granted, the patent owner may legally provide, restrict, or prohibit access to any
researcher seeking to build upon the patentee’s contribution. The researchers compared the
difference in gene patent paper citations in the pre- and post-grant period for those affected
by the patent grant to the same difference for unaffected gene paper citations. The results of
their study found that the negative impact of patent grant on the future public knowledge
production, as measured by the annual rate of forward citations to the paired paper, was
17%. A more stringent interpretation of the results showed a 5% decline in the expected
rate of citations. This more stringent interpretation suggests that follow-on genetic re-
searchers forego approximately one in ten research projects because of the causal impact
of the gene patent grant. (Declaration of Fiona E. Murray. 2010, ¶¶7–19, Ass’n for Molecular
Pathology v. U.S. Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2010).

36. Declaration of Fiona E. Murray. 2010, ¶¶5, 20, Ass’n for Molecular Pathology v. U.S.

Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2010).

37. Supplemental Declaration of Ellen Matloff. 2010, ¶¶4–11, Ass’n for Molecular Pathology v.

U.S. Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2010).

38. Declaration of Arupa Ganguly. 2009, ¶13, Ass’n for Molecular Pathology v. U.S. Patent

and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009).

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Perspectives on Science

123

have resulted in a decreased ability to do research (Cho et al. 2003). Virtually
none (less than 1%) of the respondents believed that patents had resulted in
more sharing of information among researchers, and only 3% were of the
view that patents had resulted in an increased ability to do research. A second
study concluded by the American Society of Human Genetics reported
that 46% of respondents believed that gene patents delayed or limited their
research (Rabino 2001).

When a single entity holds a monopoly on genes, others are not able to
do independent genetic testing for research purposes. University research
laboratories are arguably in a better position to investigate the thousands
of BRCA variants of unknown signiﬁcance to determine their association
with cancer than is Myriad. As Harry Ostrer stated, “By not being able to
do independent BRCA1/2 genetic testing and analysis, the ability to deter-
mine the meaning of these unknown variants is stymied and at the whim
of Myriad’s corporate interests. It may very well not be in the ﬁnancial inter-
ests of Myriad to do further research on variants of unknown signiﬁcance
from smaller or underrepresented population groups, like racial minorities,
and thus such research would not happen at all unless another lab—and in
particular an academic lab like mine—has the opportunity to do so.”39

4.5. Effects of Gene Patents on Data Sharing

All human genomic sequence information should be freely available and in
the public domain in order to encourage research and development and to
maximize its beneﬁt to society. (The Bermuda Principles 1996).

The pace of scientiﬁc innovation is fundamentally dependent on the degree
to which ideas, knowledge and data can be freely exchanged and are widely
disseminated. Many geneticists recognized from the launching of the Human
Genome Project in 1990 that a key to its ultimate success was keeping the
genome freely available to all. In 1996, a group of 50 leading scientists in-
volved in genetic sequencing met in Bermuda and committed to a group of
principles for the sharing of genetic data. These included a commitment to
release data within 24 hours of its collection by depositing it into a public
database and to not take out patents on it. Even some private companies,
such as the pharmaceutical company Merck, agreed with the sentiment that
the human genome should remain in the public domain.40

39. Declaration of Harry Ostrer. 2009, ¶12, Ass’n for Molecular Pathology v. U.S. Patent

and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009).

40. In 1994, Merck funded a massive drive to generate sequences and place them into the
public domain (Declaration of John E. Sulston. 2009, ¶¶22, 29, Ass’n for Molecular Pathology v.
U.S. Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009)).

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Unfortunately, others, including Myriad, chose to seek and vigorously enforce
patents on genetic ﬁndings in ways that inhibited data sharing. Since 1995,
laboratories from around the world have submitted data to the Breast Cancer
Information Core (BIC), an on-line central repository for information regard-
ing mutations and polymorphisms in the BRCA genes. BIC is a critical resource
for aiding the international scientiﬁc community in identifying deleterious
mutations and determining the meaning of variants of uncertain signiﬁcance
(VUS), which are genetic variants whose clinical signiﬁcance is unknown. The
value of the BIC is tied to the amount and quality of data provided by the sci-
entiﬁc community. Developing an understanding of a particular VUS requires a
large dataset that can best be obtained by pooling data from multiple labs.

According to Elizabeth Swisher, a professor at the University of Washington
School of Medicine and member of the BIC steering committee since
2004, for several years, Myriad submitted mutation and variant data to the
BIC. Because Myriad controlled clinical testing of the BRCA genes in the
United States, and because more testing occurs in the U.S. than any other
country, Myriad was the largest contributor of data to the BIC. However,
beginning sometime in 2006, Myriad started withholding its data (Pollack
2011). Because of the sheer amount of data that Myriad—and only Myriad—
was in a position to collect, once it stopped contributing data, the BIC became
a far less useful tool for the international community. As Swisher explains,
while researchers do not have a formal obligation to contribute variant data
to the BIC, “each laboratory has an incentive to do so in order to beneﬁt from
the data contributed by others and to further scientiﬁc progress. This incentive
evaporates when one laboratory controls most of the data about a gene.”41

The Legal Case against Patents on Human Genes

5.
Despite longstanding and widespread public controversy over the issuance of
patents on isolated DNA, the USPTO’s policy of granting gene patents was
never tested in the courts prior to the AMP case. On May 12, 2009, the
ACLU, together with Public Patent Foundation ﬁled its case in the Southern
District of New York on behalf of twenty plaintiffs, including four national
scientiﬁc organizations, geneticists, genetic counselors, women’s health
groups, and patients. The geneticists and medical professional organizations,
such as the lead plaintiff Association for Molecular Pathology, brought the
case because they and their members had the capability and desire to conduct
BRCA genetic testing but could not do so due to the patents.42 The other

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41. Declaration of Elizabeth Swisher. 2009, ¶20, Ass’n for Molecular Pathology v. U.S.

Patent and Trademark Ofﬁce, 702 F.Supp.2d 181 (2009).

42. Complaint 2010, pp. 3–13, Ass’n for Molecular Pathology v. U.S. Patent and Trademark

Ofﬁce, “Complaint,” 702 F.Supp.2d 181 (2010; Park 2014).

Perspectives on Science

125

plaintiffs, such as the patients, sought access to genetic testing other than that
offered by Myriad. At the time of the ﬁling of the lawsuit, breast cancer
patients Lisbeth Ceriani and Patrice Fortune were not able to obtain BRCA
testing through Myriad because Myriad had not entered into a contract with
their insurance programs.43 Vicky Thomason, an ovarian cancer survivor, and
Kathleen Raker, whose mother and grandmother died of breast cancer, were
advised to obtain large rearrangement testing but could not afford the addi-
tional price charged by Myriad.44 Breast cancer survivor Genae Girard’s
request for conﬁrmatory BRCA testing was thwarted when she learned that
Myriad was the only lab in the U.S. to offer testing. And Runi Limary, an
Asian-American woman diagnosed with breast cancer in her late 20’s, sought
further testing and research after she was told that she had a BRCA variant
of uncertain signiﬁcance.45 The case challenged Myriad’s patents on two
legal grounds—invalidity under Section 101 of the Patent Act and the U.S.
Constitution.

5.1. Patent Ineligibility of Claims to Isolated DNA

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.46

Plaintiffs’ main legal challenge to the isolated DNA patents relied on
Section 101 of the Patent Act. For decades, Section 101 was viewed by the
Patent Ofﬁce and patent bar as largely irrelevant in analyzing whether a
patent is valid. After 1980, patent attorneys relied on the Supreme Court’s
decision in Diamond v. Chakrabarty to argue that patents could be obtained
on “anything under the sun made by man” (Diamond v. Chakrabarty 1980,
p. 309), including genes that had simply been removed from the cell. Plain-
tiffs scrutinized and looked beyond this simplistic rendition of Section 101.
From its earliest cases, the Supreme Court recognized that section 101 of
the Patent Act places inherent limits on patent eligibility. This recognition
was driven by a concern that patents could intrude on the “storehouse of

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43. Complaint 2010, pp. 10, 12, Ass’n for Molecular Pathology v. U.S. Patent and Trade-

mark Ofﬁce, “Complaint,” 702 F.Supp.2d 181 (2010).

44. Complaint 2010, pp. 11, 13, Ass’n for Molecular Pathology v. U.S. Patent and Trade-

mark Ofﬁce, “Complaint,” 702 F.Supp.2d 181 (2010).

45. Complaint 2010, p. 11, Ass’n for Molecular Pathology v. U.S. Patent and Trademark

Ofﬁce, “Complaint,” 702 F.Supp.2d 181 (2010).

46. U.S. Code, Title 35, Part II, Chapter 10, §101.

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The Case Against Gene Patents

knowledge of all men” (Funk Bros. Seed Co. v. Kalo Co. 1948, p. 130). Thus,
while the scope of what is patentable is broad, “[p]henomena of nature, though
just discovered, mental processes, and abstract intellectual concepts are not
patentable, as they are the basic tools of scientiﬁc and technological work”
(Mayo 2012, p. 1293). Accordingly, mere discoveries do not automatically
merit a patent even where they are extremely useful, new, or required much
effort or resources. “Thus, a new mineral discovered in the earth or a new plant
found in the wild is not patentable subject matter. Likewise, Einstein could not
patent his celebrated law that E=mc2; nor could Newton have patented the
law of gravity. Such discoveries are ‘manifestations of [… ] nature, free to all
men and reserved exclusively to none” (Diamond v. Chakrabarty 1980, p. 309).
Plaintiffs drew on principles laid out by the Supreme Court in precedent
going back 150 years, including decisions in Mayo, Diamond, Funk Brothers,
and American Fruit Growers, to make the legal case for the patent-ineligibility
of isolated DNA. Plaintiffs relied on these seminal cases, which lay out the
key clues to applying section 101, to argue that compositions of matter
are not patent-eligible unless they: (1) have markedly different characteristics
from any found in nature; (2) are based on an inventive concept; and (3) do
not foreclose use of an underlying product or law of nature.

Isolated DNA Does Not Have Markedly Different Characteristics

5.2.
from Any Found in Nature
First, Plaintiffs argued that legal precedent forbids patents on a composition
of matter unless it has markedly different characteristics from any found in
nature. In Diamond v. Chakrabarty (1980), the Court recognized the patentabil-
ity of a genetically engineered bacterium capable of breaking down crude oil.
The Court considered whether the claimed product had “a distinctive name,
character [and] use” and “markedly different characteristics from any found in
nature” (Diamond v. Chakrabarty 1980, pp. 309–10). Comparing the unpatent-
able combination of bacteria in Funk Brothers with the genetically-engineered
Chakrabarty bacterium, the Court concluded that unlike the Funk com-
bination, the latter has “markedly different characteristics from any found
in nature” and that its “discovery is not nature’s handiwork” (Diamond v.
Chakrabarty 1980, p. 310).

The combination of species produces 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. Their use in combination does
not improve in any way their natural functioning. They serve the
ends nature originally provided and act quite independently of any
effort of the patentee.

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Here, by contrast, the patentee has produced a new bacterium with

markedly different characteristics from any found in nature and
one having the potential for signiﬁcant utility. His discovery is
not nature’s handiwork, but his own; accordingly it is patentable
subject matter under section 101. (Funk Bros. 1948, p. 131 quoted
in Diamond v. Chakrabarty 1980, p. 310)

The Diamond v. Chakrabarty Court contrasted this bacterium to the bacteria
at issue in the 1948 case of Funk Brothers. There, the patent was on a com-
bination of six strains of bacteria that together allowed plants to more
efﬁciently ﬁx nitrogen from the air without mutually inhibiting each other
(Funk Bros. 1948). Although the six bacteria strains did not exist together in
nature, and although the patent holder had “isolated” and mixed the strains,
the Court held that the product was not patent eligible because the patent
holder did “not create a state of inhibition or of non-inhibition in the bacteria”
(Funk Bros. 1948, p. 130). “Discovery of the fact that certain strains of each
species of these bacteria can be mixed without harmful effect to the properties
of either is a discovery of their qualities of non-inhibition. It is no more than
the discovery of some of the handiwork of nature and hence is not patentable”
(Funk Bros. 1948, p. 131).

The focus on the differences between the natural thing and the subject
of the patent was also the mode of analysis in the early case of American
Fruit Growers, Inc. v. Brogdex Co. There, the Court similarly rejected the
patenting of a fruit that had been treated with mold-resistant borax (American
Fruit Growers, Inc. v. Brogdex Co. 1931). Although the “complete article
is not found in nature,” and despite the “treatment, labor and manipula-
tion” that produced the fruit, the Court held that it did not become
an “article of manufacture” unless it “possesses a new or distinctive form,
quality, or property” distinct from nature (American Fruit Growers, Inc. v.
Brogdex Co. 1931, pp. 11–12).

Based on this precedent, Plaintiffs argued that isolated DNA does not have
markedly different characteristics from any found in nature. Just as the fruit
and the aggregation of bacteria strains were found to be natural phenomena,
so too is isolated DNA. DNA, unlike other chemicals, stores and conveys
speciﬁc information—as dictated by the order of nucleotides—that serves
as the blueprint for all of the proteins, cells, and organs that make up the
human body. While chemical molecules like water can be described as
H2O, HOH, or OH2 because they consist of any two hydrogen atoms and
an oxygen atom, DNA is not described according to the sugars and phos-
phates of its backbone, but by the ordering of its nucleotide sequence.
Because this blueprint is the deﬁning characteristic of DNA and remains
the same before and after isolation, isolated DNA has neither a distinctive

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The Case Against Gene Patents

name, character, nor use from naturally occurring DNA nor markedly differ-
ent characteristics. Both are DNA, their chemical structures are not markedly
different, the protein coded for by each is the same, and their use in storing
and transmitting information about a person’s heredity is identical. Isolated
DNA contains all the genetic information necessary to transmit a trait. It is
useful because the sequence—the result of “nature’s handiwork”— informs
the medical professional about how the gene operates in one’s body. If isolated
DNA had markedly different characteristics from DNA in the body, or if it
were different in name, character, and use, it would be of no diagnostic value
to medical professionals.

Isolated DNA Is Not Based on an Inventive Concept

5.3.
Second, Plaintiffs argued that Myriad’s patents were not based on an inven-
tive concept. Key to the Supreme Court’s Section 101 analysis has been
whether the thing can truly be considered an invention or a product of nature.
“‘[T]he relevant distinction’ for purposes of §101 is not ‘between living and
inanimate things, but between products of nature, whether living or not, and
human-made inventions’.” In Mayo, the Court asked, does the patent claim
arise from an “‘inventive concept’, sufﬁcient to ensure that the patent in
practice amounts to signiﬁcantly more than a patent upon the natural law
itself?” (Mayo 2012, p. 1294). Does it “add enough” or “simply append
conventional steps, speciﬁed at a high level of generality, to laws of nature
[or] natural phenomena”? (Mayo 2012, p. 1300). The Court invalidated
Prometheus’ patents on methods of ascertaining the efﬁcacy of a drug used
to treat autoimmune disorders, concluding that nothing of signiﬁcance was
added to the law of nature—the relationship between certain metabolite
levels and drug efﬁcacy in a patient (Mayo 2012, p. 1297). The Federal Cir-
cuit had upheld the patents because the method included administering the
drug to a patient and determining the resulting metabolite levels—both
steps that it found created a “transformation” that brought the claim within
the realm of human invention (Prometheus Laboratories v. Mayo Collaborative
Servs. 2009, p. 1346). However, the Supreme Court dismissed the trivial
nature of these “transformations” (Mayo 2012, p. 1303). The steps of
administering a drug and determining metabolite levels were routine, con-
ventional science (Mayo 2012, pp. 1297–8). The only addition in the patent
claim was the identiﬁcation by Prometheus of the metabolite levels that
indicate drug efﬁcacy (Mayo 2012, pp. 1297–8). The claims simply “inform
a relevant audience about certain laws of nature.”

Plaintiffs relied on Mayo’s logic to contend that isolated DNA was not
based on an inventive concept. The process of isolation was discovered long
before Myriad identiﬁed the genes, and was considered routine, conventional

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129

science even at that time. Myriad’s claims simply informed the scientiﬁc
community about the naturally occurring sequence of the BRCA1 and
BRCA2 genes. Moreover, while Myriad’s patents laid claim to any use of
every person’s BRCA1 and BRCA2 genes, its patents disclosed the sequences
of only a few of the millions of possible sequences that actually exist in the
human population as a result of human variability.

5.4. Patents on Isolated DNA Preempt Use of People’s Genetic
Information—a Product and Law of Nature
Third, Plaintiffs drew on the Supreme Court’s decisions in Mayo, Funk
Brothers, and other cases to emphasize that patents are invalid if they pre-
empt all use of a product or law of nature. In Mayo, the Court explained
that a key aspect of the Section 101 analysis turns on whether the patent
preempts use of a law or product of nature. Does the patent “risk dispro-
portionately tying up the use of the underlying natural laws, inhibiting
their use in the making of further discoveries [… ] relative to the contri-
bution of the inventor?” (Mayo 2012, pp. 1294, 1303). Ultimately, the
Court was troubled that Prometheus could prevent others, such as Mayo,
from using the relationship between metabolite levels and drug efﬁcacy—
a law of nature—to further reﬁne testing. The patents “foreclosed more
future invention than the underlying discovery could reasonably justify”
(Mayo 2012, p. 1302). Similarly in Funk Bros., the Court struck down pat-
ents that would give the patentee a monopoly on a natural phenomenon.
The Court said that qualities of the bacteria, “like the heat of the sun,
electricity, or the qualities of metals, are part of the storehouse of knowl-
edge of all men. They are manifestations of laws of nature, free to all men
and reserved exclusively to none” (Funk Bros. 1948, p. 130)47

Plaintiffs reasoned that claims on isolated DNA preempt use of a prod-
uct of nature. The patent claims themselves deﬁne isolated DNA accord-
ing to naturally occurring biological qualities—namely, that it codes for
a naturally occurring polypeptide or has a naturally occurring nucleotide
sequence. Because DNA is also a blueprint for the cell, claims on “isolated
DNA” preempt a law of nature—a piece of the genetic code. That code is
determined by biology; Myriad did not invent the length, composition, or

47. Other cases similarly discuss this concern. In Bilski v. Kappos (2010), the Court
disapproved of patents because “[a]llowing petitioners to patent risk hedging would pre-
empt use of this approach in all ﬁelds, and would effectively grant a monopoly over an
abstract idea” (Bilski v. Kappos 2010, p. 3231). And in O’Reilly v. Morse (1853), the Court
stated the patentee’s claim on any machinery or process using electric current to mark char-
acters at a distance “shuts the door against inventions of other person [… ]. ” (O’Reilly v.
Morse 1853, p. 113).

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The Case Against Gene Patents

function of the BRCA1 or BRCA2 genes. And because isolation is required
to study or use the genes, the claims preempted all scientiﬁc access to them.
These claims prevented others from isolating the patented gene, and deter-
mining its sequence of nucleotides, for every person in the United States.
Thus, patents on isolated DNA set up exclusive rights over a segment of each
person’s genetic code, blocking the law of nature consisting of the DNA
sequence and its blueprint for the operation of human cells.

5.5. Complementary DNA (cDNA)
Although Myriad did not assert in the district court or the Federal Circuit
that any of the challenged claims was limited to cDNA, the patent-eligibility
of cDNA became an issue in the case. The US government raised the issue in
its brieﬁng, as did the Federal Circuit.

cDNA, or complementary DNA, consists of the nucleotide bases that
make up DNA. cDNA is made in the laboratory when naturally occurring
mRNA, using the natural processes of the cell, acts as the template to
create the complementary DNA. Because mRNA naturally does not include
any regions that do not code for protein, the corresponding cDNA also does
not include these regions. Thus, cDNA is identical to the underlying DNA
except that the non-coding regions have been removed.

Plaintiffs argued that cDNA, when based on naturally occurring DNA
and mRNA, is not patent-eligible under Section 101. Plaintiffs con-
tended that cDNA does not have markedly different characteristics from
any found in nature, because its sequence is dictated by naturally occur-
ring DNA and mRNA. Both DNA and cDNA have similar functions:
they both encode for the same protein. Plaintiffs also asserted there was
no inventive concept with claims on cDNA that are based on naturally
occurring DNA and mRNA. Myriad did not invent the process of making
cDNA, and the fact that cDNA is made in a laboratory cannot alone
satisfy the inventiveness inquiry. Presumably, the fruit at issue in American
Fruit Growers was not treated while still on the tree, or the bacteria of
Funk Brothers isolated and aggregated in their natural habitat. Lastly, cDNA
is a basic scientiﬁc tool that serves as the bases for much genetic research.
Many genetic engineering experiments involve producing and tinkering
with cDNA. While any resulting genetically modiﬁed molecules could be
patent-eligible, patenting the underlying cDNA itself preempts this type
of innovation.

5.6. The Patent-Ineligibility of Claims on Comparing DNA Sequences
Plaintiffs also argued that a number of claims on generic methods for
comparing two genetic sequences are invalid under Section 101. Myriad
had asserted these claims when sending cease-and-desist letters to other

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laboratories. These claims are signiﬁcant because they covered comparing
genetic sequences regardless of whether one had actually performed the
isolation or sequencing of the genes. They thereby interfered with scientiﬁc
activities beyond direct uses of the isolated DNA.

Over the years, the Supreme Court consistently has applied section 101
to invalidate method claims that seek to monopolize abstract ideas or laws
of nature. In Mayo, the Court relied on the reasoning of Bilski (Bilski v.
Kappos 2010, pp. 3229–31; Gottschalk v. Benson48; Parker v. Flook49;
Diamond v. Diehr 1981) to invalidate a method claim, concluding that the
method monopolized a law of nature (Mayo 2012, p. 1297). In these cases,
The Court stated that limiting the application of an idea to a particular ﬁeld,
or adding insigniﬁcant steps, is insufﬁcient to permit patents on what would
otherwise be unpatentable (Mayo 2012, p. 1298).

Plaintiffs cited this precedent to assert that the challenged method claims
in AMP patent an abstract idea and law of nature. Five of these claims involve
the comparing or analyzing of two genetic sequences (Patent No. 5,809,999,
Claim 1; Patent No. 5,710,001; Patent No. 5,753,441; Patent No. 6,033,857,
Claims 1, 2). Claim 1 of Patent ‘857 states:

A method for identifying a mutant BRCA2 nucleotide sequence in
a suspected mutant BRCA2 allele which comprises comparing the
nucleotide sequence of the suspected mutant BRCA2 allele with the
wild-type BRCA2 nucleotide sequence, wherein a difference between
the suspected mutant and the wild-type sequence identiﬁes a mutant
BRCA2 nucleotide sequence.

The idea here—the comparing of one sequence to a reference wild-type se-
quence to identify differences or mutations—is applied to BRCA2 sequences.
But as the Supreme Court has instructed, limiting the application of an idea
to a specific situation is insufficient. “Flook rejected ‘[t]he notion that post-
solution activity, no matter how conventional or obvious in itself, can trans-
form an unpatentable principle into a patentable process.’ [… ] Flook stands
for the proposition that the prohibition against patenting abstract ideas
‘cannot be circumvented by attempting to limit the use of the formula to a

48. In Gottschalk v. Benson, the Supreme Court invalidated a patent on a method of program-
ming a digital computer, ﬁnding that the patent in essence was on a mathematical algorithm
(Gottschalk v. Benson 1972, pp. 71–2).

49. In Parker v. Flook (1978), the Supreme Court invalidated a patent on a method for
updating alarm limits during the catalytic chemical conversion of hydrocarbons, often per-
formed in oil reﬁning. The Court concluded that the patent claimed an algorithm, even
though the method included steps for adjusting the alarm limit following the application
of the algorithm, noting that the addition of post-solution activity could not transform an
unpatentable principle into a patentable process (Parker v. Flook 1978, pp. 590–95).

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particular technological environment’ or adding ‘insigniﬁcant postsolution
activity’” (Bilski v. Kappos 2010). Mayo further clariﬁed that the addition
of routine, conventional scientiﬁc steps do not create a patent-eligible inven-
tion, and trivial transformation cannot trump the law of nature doctrine
(Mayo 2012).

Plaintiffs pointed to the Supreme Court precedent to establish that the
method claims clearly cover a phenomenon of nature—whether two BRCA
sequences are different or the same. Most of the method claims cover any
comparison of two BRCA1/2 sequences for any purpose, including com-
parisons to determine predisposition to other diseases like prostate and
pancreatic cancers.50 Furthermore, claim 2 of Patent ‘857 covers com-
paring a BRCA2 sequence from a sample with the wild-type sequence,
wherein any alteration indicates a predisposition to breast cancer, and
further illustrates how the claim preempts use of a law of nature. The
claim does not specify which alterations are covered and makes the scien-
tiﬁcally incorrect assumption that any alteration indicates cancer predis-
position. Thus, a scientist who wants to identify which alterations in
fact indicate a breast cancer predisposition will run afoul of the patent claim
as soon as he or she compares two gene sequences and considers the signif-
icance of an alteration.

Plaintiffs further contended that the challenged claims could be violated
by mental processes or “mere inspection” (Prometheus Laboratories 2009,
p. 1347; Mayo 2010). One can do a side-by-side comparison of two given
sequences by visual scan or use a simple program51, or another algorithm.
Nothing in the claims precludes the use of one or more of these methods.
Moreover, the claims would cover the “comparing” of the BRCA section of
a patient’s entire genomic sequence with the reference sequence, even though
the geneticist doing the comparing had not performed the underlying
sequencing or ever “isolated” the DNA, and even though Myriad did not
offer whole genome sequencing. These claims, analyzed in their entirety,
are directed at noting differences between two sequences, a mental process
analogous to what occurs in the “wherein” clauses of Prometheus’ claim
(Mayo 2012). Moreover, even if the claims included isolating and/or sequenc-
ing steps, they would still be vulnerable under Mayo because those steps are
routine, conventional science and simply “pick out the group of individuals
likely interested in applying the law of nature” (Mayo 2010, pp. 1297–1298,
1303).

50. See Gottschalk v. Benson, 1972, 409 U. S. pp. 63, 67, 72 (observing that “[p]henomena
of nature, though just discovered, mental processes, and abstract intellectual concepts” are not
patentable because they “wholly preempt” the public’s access to the “basic tools of scientiﬁc
and technological work”).

51. See Basic Local Alignment Search, http://blast.ncbi.nlm.nih.gov/Blast.cgi.

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5.7. The Question of USPTO Deference and Industry Reliance
In bringing the case, Plaintiffs faced a major hurdle: the position of the U.S.
Patent and Trademark Ofﬁce, which approved thousands of patents on iso-
lated DNA and issued guidelines concluding it is patent-eligible (USPTO
2001, p. 1093). This practice resulted in thousands of gene patents, held
and relied upon by many different entities. Plaintiffs argued against de-
ferring to the Patent Ofﬁce by pointing to the law rejecting any such
deference, the weak legal basis for the Patent Ofﬁce’s position, and the ar-
guments adopted by the U.S. government in the litigation.

First, as a legal matter, the courts have not deferred to the USPTO’s inter-
pretations of the substantive standards set out by the Patent Act (Arnold P’ship
v. Dudas 2004, p. 1340). Instead, Congress created a presumption of validity
for issued patents.52 Forty percent of patents, once challenged in the courts,
have been found invalid, demonstrating that this presumption is often over-
come and that the respect afforded to the USPTO is far from absolute.53

Skepticism about USPTO patent grants is also warranted in light of its
historical practice. In 1984, just as it was beginning to issue patents relat-
ing to DNA molecules—such as recombinant DNA vectors—following the
Chakrabarty decision, it also issued patents that claimed genes directly,
without even the superﬁcial limitation of isolation or puriﬁcation.54 By grant-
ing patents on genes themselves, the USPTO clearly violated the bounds of
section 101 and the unanimous consensus that genes are not patentable.

Moreover, Plaintiffs pointed out that the legal reasoning behind the
USPTO’s position was weak. In issuing its guidelines on gene patents, the
USPTO cited two authorities (USPTO 2001, pp. 1092–3). It ﬁrst pointed to
the patent that had been granted to Louis Pasteur on puriﬁed yeast. The
Pasteur patents, however, were never enforced and were later acknowledged
to be invalid under American Fruit Growers by Pasquale J. Federico, later the
Commissioner of Patents and the principal drafter of the 1952 Patent Act
(Federico 1937). Secondly, the USPTO relied on Learned Hand’s 1911

52. U.S. Code, Title 35, Part III, Chapter 29, §282. http://www.law.cornell.edu/uscode/

text/35/282 (accessed 27 April 2014)

53. Institute for Intellectual Property & Information Law 2011, University of Houston
Law Center, Patstats. org, Full Calendar Year 2011 Report, http://www. patstats. org/
2011_Full_ Year_Report. html (indicating that 37% of all patents challenged on obviousness
grounds were held invalid). See also Paul F. Morgan and Bruce Stoner 2004 (citing USPTO
statistics showing that 74% of patents previously issued by the Patent Ofﬁce later challenged
through the reexamination process were either canceled or changed by the USPTO, meaning
their original approval was undeserved).

54. For example, Patent No. 4,472,502 dated September 18, 1984, claimed: “A DNA
sequence encoding a polypeptide having ability to convert L-malate into L-lactate, said
sequence being derived from Lactobacillus and having a length of about 5 kbp or less.” This
gene was useful because it controls malolactic fermentation, a natural process for wine-making.

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Parke-Davis decision and its statement that “even if [the 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. 1911)
The statement was made in dicta, but in any case has clearly been superceded
by the Supreme Court’s ruling in cases like Mayo, Chakrabarty, Funk Brothers,
and American Fruit Growers, discussed above.

Indeed, the USPTO was not the only agency with relevant expertise on
the issue of whether genes should be patented. The United States, in its
amicus brief, rightly noted that the issue of subject matter eligibility of
isolated DNA turns on questions that implicate the expertise and respon-
sibilities of a wide array of federal agencies and components, including the
USPTO, the National Institutes of Health, the Antitrust Division of
the Department of Justice, the Centers for Disease Control and Prevention,
the Ofﬁce of Science and Technology Policy, and the National Economic
Council, among others.55 The USPTO should not dictate the patent-
eligibility of genes when other agencies have at least as much insight into
whether isolated DNA is markedly different from DNA in the body,
whether isolated DNA is truly a human-made invention, and whether
patents on isolated DNA would interfere with the storehouse of knowledge.
Finally, Plaintiffs argued that industry reliance alone cannot save other-
wise invalid patents. The Supreme Court made clear in its prior ﬁndings that
the Section 101 threshold is not impacted by the interests of industry or the
longstanding existence of certain patents. In Mayo, the Court discussed the
arguments made by Prometheus and others that industry relied upon and
needed these types of patents, patents that had been issued for many years
by the USPTO.56 It found that the Section 101 question must be decided
independent of such concerns (Mayo 2012, p. 1293). In Mayo, as in Bilski,
the Court’s rulings to invalidate the patents affected a large number of other
current patents, but this impact did not sway the Court. And the Supreme
Court, in recognizing the patent eligibility of the Chakrabarty bacterium,
reversed the USPTO’s policy of refusing to grant patents on living organisms
(Diamond v. Chakrabarty 1980, p. 318). No deference to the USPTO was
warranted in the Court’s view.

5.8. Constitutional Arguments
In deciding to bring a challenge to gene patents, the ACLU was particu-
larly motivated by constitutional concerns. Gene patents raise interrelated

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55. “Brief for the United States as Amicus Curiae in Support of Neither Party,” Ass’n.

for Molecular Pathology v. U. S. Patent and Trademark Ofﬁce, 653 F. 3d 1329 (2010).

56. Biotechnology Industry Organization. 2013. “Brief for Amicus Curiae the Biotech-

nology Industry Organization in Support of Respondents,” No. 12-398 (2013).

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135

constitutional issues under the Patent Clause and the First Amendment.
The ACLU’s investigation into the problems raised by gene patents led
to the creation of the ACLU’s ﬁrst policy statement on the proper function
of the patent system within our constitutional framework, as well as the
ﬁrst patent lawsuit ever ﬁled by the ACLU. Plaintiffs argued that gene
patents violate the constitutional limitations placed on patents by each
of these provisions because they do not promote the progress of science
and useful arts and instead impede scientiﬁc inquiry and create monopolies
on information and knowledge.

The legal structure of intellectual property is created by Article I, sec-
tion 8, clause 8, which covers copyright and patents: Congress has the
power “[t]o promote the Progress of Science and useful Arts, by securing
for limited Times to Authors and Inventors the exclusive Right to their re-
spective Writings and Discoveries” (U.S. Constitution, article I, §8, clause 8).
Implicit in this provision is the recognition that before monopolies—in the
form of patents —can be approved, they must further progress. Supreme
Court Justices have recognized this limitation. In Lab. Corp. of Am. Holdings v.
Metabolite Labs., Inc., Justice Breyer wrote: “[S]ometimes too much patent
protection can impede rather than ‘promote the Progress of Science and
useful Arts’” (Lab. Corp. 2006, pp. 126–7). Justice Douglas wrote at length
about the relationship between the Constitution, the progress of science and
patenting:

It is worth emphasis that every patent case involving validity
presents a question which requires reference to a standard written
into the Constitution. Article I, s 8, contains a grant to the Congress
of the power to permit patents to be issued. But unlike most of
the speciﬁc powers which Congress is given, that grant is qualiﬁed.
The Congress does not have free reign, for example, to decide that
patents should be easily or freely given. The Congress acts under
the restraint imposed by the statement of purpose in Article I,
s 8. The purpose is “To promote the Progress of Science and useful
Arts.” The means for achievement of that end is the grant for a
limited time to inventors of the exclusive right to their inventions.
(A. & P. Tea Co. 1950, p. 154–5)

He stressed: “The standard of patentability is a constitutional standard; and
the question of validity of a patent is a question of law” (A. & P. Tea Co. 1950,
p. 156).

Plaintiffs also invoked the First Amendment as relevant to the constitu-
tional inquiry when examining gene patents. Like other legislative powers
conferred by Article I, the power to award copyrights and patents is limited
by the First Amendment.

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In copyright, where the potential conﬂict between the First Amendment
and intellectual property is more obvious, the Supreme Court has suggested
that the First Amendment requires certain doctrines, like the idea/expression
distinction, to be incorporated into statute (Harper & Row Publishers, Inc.
1985, p. 556; Eldred 2003, p. 219; Salinger 2009, p. 255; Maxtone-Graham
1986, p. 1435; Lee 2013, pp. 9–10). There can be little doubt that patenting
of abstract ideas or an entire body of knowledge would violate the First
Amendment (Ashcroft 2002, p. 253; Palko 1937, pp. 326–7; Reidel 1971,
pp. 355–6; Lee 2013, pp. 28–9). Foundational to the First Amendment is
the right to scientiﬁc inquiry (Francione 1987, pp. 428–9; Robertson 1977,
pp. 1217–18; Griswold 1965, p. 1482; Epperson 1968, pp. 100–101).

Plaintiffs pointed to these constitutional limitations to oppose the method
claims challenged in the case as covering pure thought. None of the method
claims speciﬁed a particular process for comparing or analyzing gene sequences
or testing therapeutics. Instead, they simply instructed that one sequence
from a sample should be compared to another, typically the wild-type
sequence, without stating how the comparison should be carried out. The
only instructive part of these claims is that at the end, the medical profes-
sional notes whether these two sequences are the same, different, or different
in a way that may be correlated with cancer risk. In other words, Myriad pat-
ented a thought, not an inventive process. Plaintiffs argued that because these
claims exclude others from considering the signiﬁcance of differences in the
sequences and whether a particular variant is correlated with cancer, or any
other disease, they violate both the First Amendment and Article I.

Plaintiffs further asserted that the isolated DNA claims violate Article I and
the First Amendment. The doctrine that prevents the patenting of natural
phenomena, abstract ideas, and products and laws of nature is partially pre-
mised on the observation that it is impossible to invent around those things; as
such, patenting them would not advance the useful arts. For a typical down-
stream invention, such as a carburetor, once the patent is published, others can
try to build a better carburetor using different materials or methods. Yet, once
a human gene is patented, nobody can invent a new gene that encodes for the
protein as it does in the body. And beyond acting as a barrier to an individual’s
sequence information, these patent claims prohibit the accumulation of
knowledge regarding the functioning of a certain gene at a population level.
Rather than leading to a greater understanding or a better product, isolated
DNA claims exclude others from further work with these genes and thus
give entire control over a body of knowledge to the patent holder.

6. Court Rulings
In March 2010, U. S. District Judge Robert Sweet of the Southern District
of New York granted plaintiffs’ motion and denied Myriad’s motion for

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summary judgment, concluding that none of the claims survived section 101
(Ass’n for Molecular Pathology v. US Patent and Trademark Ofﬁce 2010,
p. 238).57 He emphasized the informational nature of DNA, and concluded
that the challenged composition claims covered products and laws of nature,
as isolated DNA embodies the same genetic code as DNA in the body. He
further found that the challenged methods covered abstract ideas. Judge
Sweet carefully considered the evidence regarding whether these patents
impede the progress of science, ultimately stating that these questions could
not be resolved on summary judgment (Ass’n for Molecular Pathology 2010,
p. 220). Because he had invalidated all of the claims under the Patent Act,
Judge Sweet dismissed without prejudice the constitutional claims against
the USPTO (Ass’n for Molecular Pathology 2010, pp. 237–8).

Myriad appealed to the U.S. Court of Appeals for the Federal Circuit. In
a signiﬁcant move, the United States ﬁled an amicus brief at this stage,
arguing that isolated DNA is not patent-eligible. The government thus
took a position directly opposing its own Patent Ofﬁce. The Solicitor
General stated: “We couldn’t write a brief that allowed the patentability of
isolated DNA, for to do so would be to make lithium patentable, uranium,
coal from the earth, and a whole variety of other substances [… ]. It was
just impossible to do given the Supreme Court’s clear guidance ” (Katyal
2011).

In July 2011, the Federal Circuit issued a split decision, reversing in part
the District Court’s opinion. The Federal Circuit unanimously upheld Judge
Sweet’s ruling as to the majority of the method claims,58 concluding there
was no transformation that could render the claims patent eligible (Ass’n for
Molecular Pathology 2011, p. 1329). This ruling was not appealed by Myriad,
and thus remains binding precedent as to those claims. However, two of
the three judges—Judges Lourie and Moore—upheld the patents on “isolated
DNA.” Judge Lourie focused on what he perceived to be chemically dif-
ferent about isolated DNA, ﬁnding that because covalent bonds are broken
when DNA is isolated, isolated DNA is a patent-eligible composition (Ass’n
for Molecular Pathology 2011, pp. 1348–54, 1357). Judge Moore made addi-
tional arguments, holding that DNA segments as short as 15 nucleotides are
patent-eligible because they can be used as primers and probes in the process
of genetic testing (Ass’n for Molecular Pathology 2011, pp. 1362–65). She ex-
pressed doubt about the patent eligibility of isolated full-length genes but

57. This was Judge Sweet’s second ruling in the case. He had previously denied defendants’
motions to dismiss, which primarily argued that plaintiffs lacked legal standing to bring the
case (Ass’n for Molecular Pathology v. U.S. Patent and Trademark Ofﬁce 2009).

58. The Federal Circuit did uphold one method claim invalidated by Judge Sweet,

claim 20 of patent ‘282.

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nonetheless held that the patents were valid because industry had relied on
USPTO practice for many years (Ass’n for Molecular Pathology 2011, p. 1367).
Judge Bryson dissented, noting that “Myriad is claiming the genes them-
selves, which appear in nature on the chromosomes of living human beings”
(Ass’n for Molecular Pathology 2011, p. 1375). All three judges agreed that
cDNA, or complementary DNA, is patent-eligible under Section 101, al-
though Judge Bryson speciﬁcally found that claim 6 of Patent ‘282, which
he considered to be claiming cDNA, was not valid because it also claimed
genomic DNA. (Ass’n for Molecular Pathology 2011, pp. 1378–79).

Plaintiffs sought review by the Supreme Court. While the petition was
pending, the Supreme Court issued a decision in Mayo v. Prometheus, where
it unanimously invalidated method claims for assessing a patient’s reaction
to a drug because they covered laws of nature. It then vacated the Federal
Circuit’s decision and ordered further consideration in light of Mayo. How-
ever, upon remand, the divided Federal Circuit issued decisions echoing its
ﬁrst rulings, with the majority suggesting that Mayo had little impact on
AMP (Ass’n for Molecular Pathology 2012). The plaintiffs ﬁled a second peti-
tion with the Supreme Court, and the Court granted the petition to review
this question: Are human genes patentable?

On June 13, 2013, a unanimous Supreme Court answered with a resound-
ing “no”: A naturally occurring DNA segment is a product of nature and not
patent eligible merely because it has been isolated. Moreover, “Myriad did
not create anything. To be sure, it found an important and useful gene,
but separating that gene from its surrounding genetic material is not an
act of invention” (Ass’n for Molecular Pathology 2013, p. 2117). The
“isolation” of the genes did not create an invention, because what Myriad
had patented was the “genetic information encoded in the BRCA1 and
BRCA2 genes” (Ass’n for Molecular Pathology 2013, p. 2118). “[I]ts claim is
concerned primarily with the information contained in the genetic sequence,
not with the speciﬁc chemical composition of a particular molecule” (Ass’n for
Molecular Pathology 2013, p. 2118). Moreover, “the processes used by Myriad
to isolate DNA were well understood by geneticists at the time of Myriad’s
patents ‘were well understood, widely used, and fairly uniform insofar as any
scientist engaged in the search for a gene would likely have utilized a similar
approach’” [sic] (Ass’n for Molecular Pathology 2013, pp. 2119–20).

The Court also ruled that cDNA is not a product of nature, with an im-
portant caveat: “except insofar as very short series of DNA may have no in-
tervening introns to remove when creating cDNA. In that situation, a short
strand of cDNA may be indistinguishable from natural DNA.” (Ass’n for
Molecular Pathology 2013, 2119). The Court stated that it was not expressing
an opinion on whether patents on cDNA satisfy other statutory require-
ments of patentability, citing to possible grounds of invalidity including

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sections 102, 103, and 112 of the Patent Act (Ass’n for Molecular Pathology 2013,
2119 n. 9).

The Supreme Court agreed with the Plaintiffs that it owed no deference
to the USPTO. The Court noted that Congress had never endorsed the
USPTO’s view on gene patents, and that the United States as amicus curiae
not only disagreed with the USPTO’s position but also had argued that
“the USPTO’s practice was not ‘a sufﬁcient reason to hold that isolated
DNA is patent-eligible’” (Ass’n for Molecular Pathology 2013, p. 2119). The
Court further rejected Myriad’s arguments that the patents should be upheld
to avoid disturbing the reliance interests of patent holders (Ass’n for Molecular
Pathology 2013, p. 2119 n7).

None of the courts ruled on the merits of the Plaintiffs’ constitutional
arguments. Judge Sweet dismissed the constitutional claims against the
USPTO based on the doctrine of constitutional avoidance (Ass’n for Molecular
Pathology 2010, pp. 237–8). Because he ruled in Plaintiffs’ favor in invali-
dating all of the challenged patent claims, he declined to decide the consti-
tutional questions that were raised. Plaintiffs continued to raise the First
Amendment argument against the University of Utah defendants through-
out the litigation; however, neither the Federal Circuit nor Supreme Court
addressed it. Yet, it is clear that the invalidation of the isolated DNA claims
by the Supreme Court and of the screening method claims by the Federal
Circuit pursuant to Section 101 was rooted in a fundamental objection to
allowing patent claims that would dictate access to genetic information
and abstract thought, thereby impeding scientiﬁc progress and controlling
scientiﬁc inquiry.

7. Conclusion: Implications and Lessons Learned
The implications of the Court’s decision are vast: for one, as a result of the
ruling, Myriad will no longer maintain a legal monopoly over any use
of the BRCA1 and BRCA2 genes, nor should it be able to dictate the
standard of care and extent of testing for these genes. The impacts of
the ruling for breast cancer predisposition testing were demonstrated
almost immediately after the decision was issued: within 24 hours, at least
5 labs announced that they would begin offering testing for the BRCA1
and BRCA2 genes (Pollack 2013). Some of the labs promised to offer
testing at a lower price than Myriad’s. The University of Washington an-
nounced that it would take steps to immediately add BRCA1 and BRCA2
to the multi-gene panel offered by its lab in order to provide a more person-
alized assessment of cancer risk than is currently offered through Myriad’s
testing program. Currently several labs provide BRCA testing, including
two of the largest—LabCorp and Quest Diagnostics.

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The Case Against Gene Patents

The Court’s decision reaches far beyond Myriad, of course. The decision
rightly invalidates all existing claims to naturally occurring DNA sequences
and should prevent future claims of this sort to be granted.59 More broadly,
the Court’s ﬁnding reafﬁrms the vitality of section 101. Along with American
Fruit Growers, Funk Brothers, and Chakrabarty, the ruling reestablishes, con-
sistent with precedent, that something is not a patent eligible composition
simply because it is removed from its natural environment or commercially
useful, or required intensive work and resources. It clariﬁes that Chakrabarty
did not bestow blanket section 101 approval on all compositions related to
biotechnology but only on those that are markedly different from their
naturally occurring form. And it recognizes that some things, in order to
promote the progress of science, must be free to all to use.

Coupled with Mayo, AMP legally prohibits patents that interfere with
using products and laws of nature for basic scientiﬁc work and clears away
the patent thicket that previously impeded laboratories from engaging in
genetic testing. Under the two decisions, patent claims on isolated DNA
as well as routine methods for comparing genes or identifying mutations
are clearly invalid under Section 101. To hold otherwise would be “to
permit patent claims to tie up too much use of laws of nature” (Mayo 2012,
p. 1302).

While any fair application of the Court’s unanimous decisions in these
cases would render invalid patent claims that grant exclusive rights to
examining a gene or prevent others from developing alternative testing
methods, the thousands of patents of this type that were issued by the
USPTO in the decades before these decisions were rendered are not
automatically invalidated based on the rulings. No doubt there will con-
tinue to be litigation in this area as patentees seek to defend existing
patent rights and test the limits of what is now patent-eligible with the
USPTO.

Indeed, within a few weeks of the Court’s decision, Myriad ﬁled suit
against two laboratories in an attempt to reassert its monopoly on BRCA
testing. Each of the laboratories—Ambry Genetics and Gene by Gene—
had begun or planned to offer BRCA-related testing. Myriad asserted that
the labs were infringing its patents, citing claims that were not the subject
of the AMP suit but should clearly be invalid under the Supreme Court’s
decisions in Mayo and AMP and the Federal Circuit’s ruling in AMP on the
method claims (American Civil Liberties Union et al. 2013). Other labs

59. Though Plaintiffs disagreed with the Court’s ruling on cDNA, that aspect of the
decision had little impact on the ultimate goals of the case. One does not need to use cDNA
in order to conduct genetic testing, and the Court’s decision made clear that the ultimate
patentability of cDNA is still an unresolved question.

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Perspectives on Science

141

offering BRCA testing are also involved in the litigation. In Re: BRCA1–
and BRCA2–Based Hereditary Cancer Test Patent Litigation 2014. It is
unclear whether this latest litigation is simply a tactic by Myriad to scare
off its competitors, or whether it believes in the validity of the claims it
has cited. But what is clear is that the company’s actions are a real disservice
to patients, who deserve greater options to cancer predisposition testing
than the one that Myriad has offered for the past 15 years. Moreover, the
company’s audacious behavior in attempting to thwart any competitors de-
spite the Court’s clear direction in this arena underscores a fundamental
problem with the patent system as a whole: the public’s interest is often
the last interest to be served, if at all.

AMP was the ﬁrst case to challenge the legality of gene patents. The case
raised legal questions about the scope of Section 101 that were ripe for
consideration in a new era of precision medicine, and where genetic tests
are increasingly relied upon in tailoring medical treatments to individual
patients. Progress in this ﬁeld fundamentally depends upon the development
of accurate, affordable molecular diagnostics and requires that the human
genome be freely available to all. The case beneﬁtted from the collective
experiences of scientists, clinicians and patients over many years. It brought
together a large and diverse coalition that together provided strong oppo-
sition to a patent policy at odds with the system’s mission to promote the
progress of science. The case succeeded in bringing to the forefront a more
holistic understanding of how improperly issued patents can harm people
and innovation by giving voice to the full range of legal and policy argu-
ments against gene patenting. By asserting the public’s interest in ending
monopolies over genes and genetic information, the case reshaped the law
and provided a much-needed check on entrenched patenting practices. Ulti-
mately, the case serves as a model for future patent advocacy and reform in
the public interest.

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