Document ID: s3://data.kl3m.ai/documents/govinfo/USCOURTS/USCOURTS-ca13-15-01203/USCOURTS-ca13-15-01203-0/pdf.json

Parties Involved:
Bristol-Myers Squibb Company
Appellee
Genetic Technologies Limited
Appellant

Document Text:

United States Court of Appeals 

for the Federal Circuit ______________________ 

GENETIC TECHNOLOGIES LIMITED,

Plaintiff-Appellant

v.

MERIAL L.L.C., BRISTOL-MYERS SQUIBB 

COMPANY,

Defendants-Appellees

______________________ 

2015-1202, 2015-1203

______________________ 

Appeals from the United States District Court for the 

District of Delaware in Nos. 1:12-cv-00396-LPS, 1:12-cv00394-LPS Chief Judge Leonard P. Stark.

______________________ 

Decided: April 8, 2016

______________________ 

BENJAMIN B. LIEB, Sheridan Ross, PC, Denver, CO, 

argued for plaintiff-appellant. Also represented by 

ROBERT R. BRUNELLI, HIWOT M. COVELL. 

GREGORY A. CASTANIAS, Jones Day, Washington, DC, 

argued for defendant-appellee Merial L.L.C. Also represented by JOHN PATRICK ELSEVIER, PHILIP SHENG, San 

Diego, CA; JUDY CATHERINE JARECKI-BLACK, Merial 

Limited, Atlanta, GA. 

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2 GENETIC TECHNOLOGIES LIMITED v. MERIAL L.L.C. 

AMY K. WIGMORE, Wilmer Cutler Pickering Hale and 

Dorr LLP, Washington, DC, argued for defendantappellee Bristol-Myers Squibb Company. Also represented 

by THOMAS SAUNDERS, TRACEY COTE ALLEN; WILLIAM F.

LEE, ALLISON TRZOP, Boston, MA.

______________________ 

Before PROST, Chief Judge, DYK, and TARANTO, Circuit 

Judges.

DYK, Circuit Judge.

Genetic Technologies Limited (“GTG”) brought suit

against Merial L.L.C. (“Merial”) and Bristol-Myers Squibb

(“BMS”) (together, “appellees”). GTG alleged that appellees had infringed U.S. Patent No. 5,612,179 (“the ’179 

patent”), which relates to methods of detecting genetic 

variations. The district court granted appellees’ motions 

to dismiss for failure to state a claim and entered final 

judgment that claims 1–25 and 33–36 of the ’179 patent 

are ineligible for patenting under 35 U.S.C. § 101. For 

purposes of this appeal, the parties have stipulated that 

claim 1 is representative of all of the invalidated claims. 

Because we agree that claim 1 is directed to unpatentable 

subject matter, we affirm. 

BACKGROUND

The ’179 patent claims methods of analyzing sequences of genomic deoxyribonucleic acid (“DNA”). Genetic 

information is encoded in DNA, which carries instructions 

for the development and function of all life. DNA sequences spell out instructions for synthesis of shorter 

sequences of ribonucleic acid (“RNA”), which in turn 

provide templates for synthesis of proteins. An individual’s complete set of DNA is known as his genome, and a 

particular sequence of DNA within the genome that codes 

for a given protein (or functional RNA molecule) is referred to as a gene. Genes are the individual units definCase: 15-1203 Document: 11-2 Page: 2 Filed: 04/08/2016
GENETIC TECHNOLOGIES LIMITED v. MERIAL L.L.C. 3

ing heredity, and a person’s overall collection of genes is 

known as his genotype. The site on a chromosome occupied by a particular gene is the genetic locus. Genes 

typically contain both coding regions, called exons, and 

non-coding regions, called introns. Exons are regions of 

the DNA sequence of the gene that are expressed, i.e., 

ultimately “decoded” and translated into the protein 

sequence. Introns are regions that are not expressed; 

these regions do not code for protein. 

Each individual has his own unique genotype, inherited from his two parents. Variation of the precise genetic 

sequence within a particular gene among different people 

is known as genetic polymorphism, and the various alternative forms (mutations) of the gene are referred to as 

individual alleles. Detection of specific alleles can be 

useful for a variety of purposes, including diagnosis and 

treatment of genetic disorders and diseases correlated 

with those alleles, e.g., sickle-cell anemia, hemophilia, 

and cystic fibrosis. 

In the 1980s, Dr. Malcolm J. Simons, the named inventor of the ’179 patent, working with GTG,1 discovered 

an interesting feature of genomic DNA. Dr. Simons 

discovered that certain DNA sequences in coding regions 

(exons) of certain genes are correlated with non-coding 

regions (introns) within the same gene, non-coding regions in different genes, or non-coding regions of the 

genome that are not part of any gene. Non-coding DNA 

regions between genes are referred to by the ’179 patent 

as “intergenic spacing sequences” and have been referred 

to colloquially as “junk DNA,” because, at least historical1 Dr. Simons’s work was done for a predecessor 

company, GeneType, AG. For simplicity we refer to both 

GTG and GeneType as “GTG.” 

 

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ly, they appeared to serve no function. ’179 patent col. 5 

ll. 42–46.

Dr. Simons found that the correlated coding and noncoding regions tend to be inherited together, with only 

rare shuffling. In other words, the regions are in “linkage 

disequilibrium,” meaning that the coding and non-coding 

regions appear “linked” together in individuals’ genomes 

more often than probability would dictate. ’179 patent 

col. 5 ll. 20–32; see also, e.g., Henderson’s Dictionary of

Biology 366 (14th ed. 2008) (“[L]inkage disequilibrium [is 

a] condition in which certain alleles at two linked loci are 

non-randomly associated with each other.”). The correlated coding and non-coding regions may be linked even 

though the two sequences are located far apart from one 

another on the chromosome. 

Dr. Simons concluded that alleles of a particular gene 

may be detected, using well-established laboratory techniques, not by looking for the coding region of the gene 

itself but instead by amplifying and analyzing non-coding 

regions known to be linked to the coding region. Between 

1989 and 1992, Dr. Simons and GTG filed several patent 

applications related to the discovery. One of these applications ultimately became the ’179 patent. Claim 1 of the 

’179 patent recites: 

1. A method for detection of at least one coding region allele of a multi-allelic genetic locus comprising:

a) amplifying genomic DNA with a primer pair 

that spans a non-coding region sequence, said 

primer pair defining a DNA sequence which is in 

genetic linkage with said genetic locus and contains a sufficient number of non-coding region sequence nucleotides to produce an amplified DNA 

sequence characteristic of said allele; and 

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b) analyzing the amplified DNA sequence to 

detect the allele.

’179 patent col. 59 ll. 57–67. Claim 1 is thus broad in 

scope; it encompasses methods of detecting a coding 

region allele by amplifying and analyzing any linked noncoding region, which could be found within the same gene 

as the coding region, within a different gene, or within an 

intergenic region. 

According to GTG, the methods of the ’179 patent 

have various advantages over prior art methods involving 

direct analysis of a coding region. For example, GTG 

stated that “analysis of relatively short regions of noncoding sequences, of a size which can be amplified, can 

provide more information than prior art analyses such as 

cDNA RFLP analyses which involve the use of significantly larger DNA sequences . . . .” ’179 Patent Prosecution 

History, Applicant’s Amendment and Remarks of Jan. 14, 

1993, at 6. 

In 2011, GTG sued several pharmaceutical and biotechnology companies, including Merial and BMS, in the 

United States District Court for the District of Colorado

for infringement of the ’179 patent. GTG’s claims against 

Merial and BMS were severed and transferred to the 

District of Delaware. GTG alleged infringement of at

least one claim of the ’179 patent and, in BMS’s case,

infringement of a second patent not at issue in this appeal. Merial and BMS subsequently moved to dismiss 

under Federal Rule of Civil Procedure 12(b)(6) (“Rule 

12(b)(6)”) for failure to state a claim, arguing that the 

claims of GTG’s patents covered ineligible subject matter 

under 35 U.S.C. § 101. 

After briefing and oral argument, the district court

granted defendants’ motions, holding that claim 1 of the

’179 patent is invalid for claiming a law of nature, which 

is patent-ineligible subject matter. “A claim is unpatentCase: 15-1203 Document: 11-2 Page: 5 Filed: 04/08/2016
6 GENETIC TECHNOLOGIES LIMITED v. MERIAL L.L.C. 

able if it merely informs a relevant audience about certain 

laws of nature, even newly-discovered ones, and any 

additional steps collectively consist only of wellunderstood, routine, conventional activity already engaged in by the scientific community. The claim involved 

here, claim 1 of the ’179 patent, does just that and no 

more.” Genetic Techs. Ltd. v. Bristol-Myers Squibb Co., 72 

F. Supp. 3d 521, 527 (D. Del. 2014) (citing Mayo Collaborative Servs. v. Prometheus Labs., Inc., 132 S. Ct. 1289, 

1298 (2012)). The district court did not evaluate the 

validity of other claims of the ’179 patent under § 101, 

noting that GTG had not specified which of those claims it 

was asserting against Merial and BMS. 

GTG, Merial, and BMS subsequently stipulated that, 

for purposes of appeal, claim 1 is representative of claims 

2–25 and 33–36 of the ’179 patent with respect to eligibility under § 101. GTG also covenanted not to assert the 

remaining claims, 26–32, of the ’179 patent. Upon the 

parties’ request, the district court dismissed GTG’s infringement claims against Merial and BMS and entered 

judgment that claims 1–25 and 33–36 of the ’179 patent 

are invalid for claiming unpatentable subject matter. 

GTG appeals. We have jurisdiction under 28 U.S.C. 

§ 1295(a)(1). 

DISCUSSION

I 

We review de novo the dismissal for failure to state a 

claim under Rule 12(b)(6). Content Extraction & Transmission LLC v. Wells Fargo Bank, Nat’l Ass’n, 776 F.3d 

1343, 1346 (Fed. Cir. 2014); Sands v. McCormick, 502 

F.3d 263, 267 (3d Cir. 2007). Patent eligibility under 

35 U.S.C. § 101 is a question of law that we review de 

novo. OIP Techs., Inc. v. Amazon.com, Inc., 788 F.3d 

1359, 1362 (Fed. Cir. 2015); Content Extraction, 776 F.3d 

at 1346.

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We have repeatedly recognized that in many cases it 

is possible and proper to determine patent eligibility 

under 35 U.S.C. § 101 on a Rule 12(b)(6) motion. See, e.g., 

OIP Techs., 788 F.3d at 1362; Content Extraction, 776 

F.3d at 1351; buySAFE, Inc. v. Google, Inc., 765 F.3d 

1350, 1355 (Fed. Cir. 2014). In many cases, too, evaluation of a patent claim’s subject matter eligibility under 

§ 101 can proceed even before a formal claim construction. 

“[C]laim construction is not an inviolable prerequisite to a 

validity determination under § 101.” Bancorp Servs., 

L.L.C. v. Sun Life Assurance Co. of Canada (U.S.), 687 

F.3d 1266, 1273 (Fed. Cir. 2012); see also Content Extraction, 776 F.3d at 1349. Here, there is no claim construction dispute relevant to the eligibility issue. 

II

Section 101 establishes that “any new and useful process, machine, manufacture, or composition of matter, or 

any new and useful improvement thereof” may be eligible 

for a patent, subject to the conditions and requirements of 

the Patent Act. 35 U.S.C. § 101. But the Supreme Court 

has “long held that this provision contains an important 

implicit exception: Laws of nature, natural phenomena, 

and abstract ideas are not patentable.” Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 133 S. Ct. 2107, 

2116 (2013) (quoting Mayo, 132 S. Ct. at 1293). “Phenomena 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.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972). 

“Groundbreaking, innovative, or even brilliant discovery 

does not by itself satisfy the § 101 inquiry.” Myriad, 133 

S. Ct. at 2117. 

In the past several years, most notably in its Mayo

and Alice decisions, the Supreme Court has articulated a

now well-established two-step test for patent eligibility 

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under § 101. The test “distinguish[es] patents that claim 

laws of nature, natural phenomena, and abstract ideas 

from those that claim patent-eligible applications of those 

concepts.” Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 134 S. 

Ct. 2347, 2355 (2014) (citing Mayo, 132 S. Ct. at 1296–97). 

As set forth in Alice: 

First, we determine whether the claims at issue 

are directed to one of those patent-ineligible concepts. If so, we then ask, what else is there in the 

claims before us? . . . We have described step two 

of this analysis as a search for an inventive concept—i.e., an element or combination of elements 

that is sufficient to ensure that the patent in practice amounts to significantly more than a patent 

upon the ineligible concept itself. 

Id. (alterations, citations, and quotation marks omitted). 

As noted above, claim 1 of the ’179 patent is the only 

claim before us. We begin at step one of the Mayo/Alice

test and ask first whether claim 1 is directed to a patentineligible concept—e.g., a law of nature, natural phenomenon, or abstract idea. Alice, 134 S. Ct. at 2355. We find 

that it is. Claim 1 is directed to the relationship between 

non-coding and coding sequences in linkage disequilibrium and the tendency of such non-coding DNA sequences 

to be representative of the linked coding sequences—a law 

of nature. 

Claim 1 recites a method of detecting an allele of interest at a multi-allelic locus (i.e., a location on the chromosome where multiple variations of a particular gene 

are known) by amplifying a sequence of non-coding region 

DNA known to be linked with the allele and then analyzing the non-coding region to detect the allele. In somewhat plainer terms, claim 1 covers a method of detecting 

a coding region of a person’s genome by amplifying and 

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analyzing a linked non-coding region of that person’s 

genome. 

Claim 1 covers any comparison, for any purpose, of 

any non-coding region sequence known to be linked with a 

coding region allele at a multi-allelic locus. The ’179 

patent states that “[t]he method can be used to detect 

alleles of genetic loci for any eukaryotic organism,” ’179 

patent col. 4 ll. 12–13, and “is generally applicable to 

detection of any type of genetic trait,” id. at col. 46 ll. 8–9. 

The ’179 patent does not limit its scope to methods of 

detecting any particular alleles linked to any particular

non-coding sequences, although the specification does 

provide some examples of linked alleles known to be 

diagnostic of inherited diseases such as cystic fibrosis and 

muscular dystrophy. See generally, ’179 patent col. 43 

l. 43–col. 46 l. 6. Claim 1 broadly covers essentially all

applications, via standard experimental techniques, of the 

law of linkage disequilibrium to the problem of detecting 

coding sequences of DNA. 

The product of the method of claim 1 is information 

about a patient’s natural genetic makeup—at least one 

coding region allele. The claim relies on the existence of 

linkage disequilibrium between the non-coding and coding

regions—i.e., the tendency of these regions to be linked. 

Linkage disequilibrium is indisputably a universal, 

inherent feature of human DNA, and the ’179 patent itself 

notes that the claims are based on this fact. “The present 

invention is based on the discovery that amplification of 

intron sequences that exhibit linkage disequilibrium with 

adjacent and remote loci can be used to detect alleles of 

those loci.” ’179 patent col. 4 ll. 28–31.

Claim 1 of the ’179 patent is in this respect quite similar to the claims invalidated in Mayo itself. In Mayo, the 

Supreme Court considered method claims that likewise 

required analysis of a biological sample (the blood of a 

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patient being treated with a thiopurine drug) and in 

which the focus of the claimed advance over the prior art 

was allegedly newly discovered information about human 

biology: the likelihood that a patient could suffer toxic 

side effects from particular doses of the drug. Mayo, 132 

S. Ct. at 1296–97. “Claim 1, for example, states that if

the levels of 6-TG in the blood (of a patient who has taken 

a dose of a thiopurine drug) exceed about 400 pmol per 

8 x 108 red blood cells, then the administered dose is likely 

to produce toxic side effects.” Id. The Court concluded 

that the claims were necessarily directed to an underlying 

law of nature or natural phenomenon, even if implementation of the method involves substantial human labor 

and ingenuity: 

While it takes a human action (the administration 

of a thiopurine drug) to trigger a manifestation of 

this relation in a particular person, the relation 

itself exists in principle apart from any human action. The relation is a consequence of the ways in 

which thiopurine compounds are metabolized by 

the body—entirely natural processes. And so a 

patent that simply describes that relation sets 

forth a natural law.

Id. at 1297. We agree with the district court that “just as 

the relationship at issue in Mayo was entirely a consequence of the body’s natural processes for metabolizing 

thiopurine, so too is the correlation here (between variations in the non-coding regions and allele presence in the 

coding regions) a consequence of the naturally occurring 

linkages in the DNA sequence.” Genetic Techs., 72 

F. Supp. 3d at 530. 

In our court’s recent Ariosa v. Sequenom decision, we 

considered genetic testing method claims remarkably 

similar to the claim here and found, at step one of the 

Mayo/Alice test, that they too were directed to unpatentaCase: 15-1203 Document: 11-2 Page: 10 Filed: 04/08/2016
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ble subject matter. Ariosa Diagnostics, Inc. v. Sequenom, 

Inc., 788 F.3d 1371, 1373–74, 1376 (Fed. Cir. 2015). The 

claims in Ariosa covered a method of detecting fetal DNA 

by amplifying and analyzing cell-free fetal DNA 

(“cffDNA”) sampled from a pregnant woman’s blood. Id.

at 1373–74. The court found that “the claims are directed 

to matter that is naturally occurring” and that the inventors there did not purport to “create[] or alter[] any of the 

genetic information encoded in the cffDNA.” Id. at 1376. 

The focus of the claimed advance over the prior art was

allegedly newly discovered information about human 

biology: paternally inherited cffDNA is to be found in 

maternal blood (using established detection techniques). 

So too in the present case: the patent claim focuses on a 

newly discovered fact about human biology (the linkage of 

coding and non-coding regions of DNA), involves no creation or alteration of DNA sequences, and does not purport 

to identify novel detection techniques. 

The similarity of claim 1 to the claims evaluated in 

Mayo and Ariosa requires the conclusion that claim 1 is 

directed to a law of nature. The sole function of the 

“primer pair defining a DNA sequence which is in genetic 

linkage with [a multi-allelic] genetic locus” is to amplify a 

sequence of non-coding DNA in linkage disequilibrium 

with a sequence of coding DNA of interest. ’179 patent 

col. 59 ll. 60–62. “The method comprises amplifying 

genomic DNA with a primer pair that spans an intron 

sequence and defines a DNA sequence in genetic linkage 

with an allele to be detected.” Id. at col. 4 ll. 37–39. The 

claim is directed to a natural law—the principle that 

certain non-coding and coding sequences are in linkage 

disequilibrium with one another.2 We hold that claim 1 is 

2 At various points in its briefs, GTG appears to 

concede that claim 1 is directed to a law of nature. See, 

 

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directed to unpatentable subject matter at the first step of 

the Mayo/Alice test. 

III

We thus proceed to step two of the Mayo/Alice analysis. At step two, after identifying a claim directed to 

unpatentable subject matter, “we must examine the 

elements of the claim to determine whether it contains an 

inventive concept sufficient to transform the claimed 

abstract idea [or law of nature] into a patent-eligible 

application.” Alice, 134 S. Ct. at 2357 (internal quotation 

marks omitted) (citing Mayo, 132 S. Ct. at 1294, 1298). 

“The question . . . is whether the claims do significantly 

more than simply describe [a] natural relation[].” Mayo, 

132 S. Ct. at 1297. The inventive concept necessary at 

step two of the Mayo/Alice analysis cannot be furnished 

by the unpatentable law of nature (or natural phenomenon or abstract idea) itself. That is, under the Mayo/Alice 

framework, a claim directed to a newly discovered law of 

nature (or natural phenomenon or abstract idea) cannot 

rely on the novelty of that discovery for the inventive 

concept necessary for patent eligibility; instead, the 

application must provide something inventive, beyond 

mere “well-understood, routine, conventional activity.” 

Mayo, 132 S. Ct. at 1294; see also Myriad, 133 S. Ct. at 

2117; Ariosa, 788 F.3d at 1379. “[S]imply appending 

e.g., Appellant’s Br. at 8 (“The District Court found that 

the Discovery was a natural phenomenon: ‘The correlations between variations in non-coding regions of DNA—

formerly known as “junk DNA”—and variations in coding 

regions of DNA—specifically, alleles—are natural phenomena. . . .’ [T]his finding is correct . . . .”); id. at 17 

(“[T]he natural phenomenon underlying Claim 1 is the 

Discovery [of linkage disequilibrium between coding and 

non-coding regions] . . . .”). 

 

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conventional steps, specified at a high level of generality, 

to laws of nature, natural phenomena, and abstract ideas 

cannot make those laws, phenomena, and ideas patentable.” Mayo, 132 S. Ct. at 1300. Claims directed to laws of 

nature are ineligible for patent protection when, “(apart 

from the natural laws themselves) [they] involve wellunderstood, routine, conventional activity previously 

engaged in by researchers in the field.” Mayo, 132 S. Ct. 

at 1294. 

We conclude that the additional elements of claim 1

are insufficient to provide the inventive concept necessary

to render the claim patent-eligible. 

A 

We look first at the physical steps by which claim 1 

implements the natural law of linkage disequilibrium 

between coding and non-coding regions to determine 

whether they provide more than “well-understood, routine, conventional activity” already engaged in by those in 

the field. Id. Claim 1 contains two implementation steps, 

“amplifying genomic DNA with a primer pair” and “analyzing the amplified DNA sequence to detect the allele.” 

’179 patent col. 59 ll. 57–67. 

The first claimed step of “amplifying” genomic DNA 

with a primer pair was indisputably well known, routine, 

and conventional in the field of molecular biology as of 

1989, when the first precursor application to the ’179 

patent was filed. GTG concedes that “[t]he general laboratory technique of primer pair amplification of DNA, 

admittedly, was known as of the Filing Date.” Appellant’s 

Br. at 4. The ’179 patent repeatedly characterizes primer 

pair amplification as prior art. “The method is commonly 

referred to as the polymerase chain reaction sequence 

amplification method or PCR.” ’179 patent col. 2 ll. 53–

55; see also id. at col. 3 ll. 5–8 and ll. 39–45 (listing specific primer pair amplification techniques known in the art); 

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col. 12 ll. 47–64 (same). To overcome an examiner’s claim 

rejection for lack of enablement under 35 U.S.C. § 112, 

GTG expressly argued during prosecution of the ’179 

patent that “amplification . . . [was a] technique[] . . . readily practiced by those in skill at the time 

the application was filed.” ’179 Patent Prosecution History, Applicant’s Amendment and Remarks of Jan. 14, 1993, 

at 7–8. 

The second physical implementation step, “analyzing” 

amplified DNA to provide a user with information about 

the amplified DNA, including its sequence, was also 

clearly well known, routine, and conventional at the time 

the ’179 patent was filed. GTG concedes that 

“[t]echniques to analyze amplified DNA were . . . admittedly known.” Appellant’s Br. at 4. Moreover, the Background section of the ’179 patent acknowledges as prior 

art the claimed two-step combination of amplification of 

DNA and subsequent analysis of its sequence. “A number 

of techniques have been employed to detect allelic variants of genetic loci including analysis of restriction fragment length polymorphic (RFLP) patterns, use of 

oligonucleotide probes, and DNA amplification methods.” 

’179 patent col. 1 ll. 50–53; see also col. 10 ll. 6–34 (discussing methods of analyzing amplified DNA, including 

“sequencing the amplified DNA sequence”). GTG granted

during prosecution of the ’179 patent that it did not 

invent any new physical techniques. “Applicant has not 

invented a new way to analyze genetic loci. Rather Applicant has found that when prior art techniques are applied 

to the non-coding sequences, the result can be more 

informative than analysis of the coding regions.” ’179 

Patent Prosecution History, Applicant’s Amendment and 

Remarks of Jan. 14, 1993, at 6. 

Thus the physical steps of DNA amplification and 

analysis of the amplified DNA to provide a user with the 

sequence of the non-coding region do not, individually or 

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in combination, provide sufficient inventive concept to 

render claim 1 patent eligible.3 In this regard, claim 1 of 

the ’179 patent is directly comparable to the claims invalidated in Ariosa. Ariosa, 788 F.3d at 1377 (“Using methods like PCR to amplify and detect cffDNA was wellunderstood, routine, and conventional activity in 1997.”). 

B 

GTG argues that claim 1 provides more: once the noncoding DNA has been amplified and sequenced, an instruction to users to “analyz[e] the amplified DNA sequence to detect the [coding region] allele.” ’179 patent 

col. 59 ll. 66–67 (emphasis added). “[T]he analysis limitation of Claim 1 requires that analysis to be performed 

upon the amplified, i.e., man-made, non-coding DNA to 

detect the coding region allele. [This and other] limitations do not recite the Discovery [of linkage disequilibrium between coding and non-coding regions] or the 

Observation [of using a non-coding polymorphism to learn 

about a coding region allele] . . . .” Appellant’s Reply Br. 

at 15. GTG argues that, at the time the ’179 patent was 

3 We are not persuaded by GTG’s arguments that 

claim 1 is inventive because it involves analysis of manmade amplified DNA. While the man-made amplified 

non-coding DNA may have an “altered methylation status,” Appellant’s Br. at 22, its sequence is identical to that 

of naturally occurring DNA, unlike the cDNA held to be 

patent-eligible in Myriad, 133 S. Ct. at 2119. As with the 

claims to genomic DNA invalidated in Myriad, claim 1 “is 

concerned primarily with the information contained in the 

genetic sequence, not with the specific chemical composition of a particular molecule,” and any minor chemical 

differences are irrelevant. Id. at 2118; see also In re 

Roslin Inst. (Edinburgh), 750 F.3d 1333, 1337 (Fed. Cir. 

2014). 

 

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filed, “no one had before analyzed man-made non-coding 

DNA in order to detect a coding region allele,” and that 

this additional feature, at least, provides sufficient inventive concept to pass step two of the Mayo/Alice test. 

Appellant’s Br. at 4. 

We disagree. The term “to detect the allele” (in the 

sense of examining the non-coding region to detect an 

allele in the coding region) is a mental process step, one 

that provides claim 1 with a purpose but does not create 

the requisite inventive concept, because it merely sets 

forth a routine comparison that can be performed by the 

human mind. As we held in Cybersource, “[m]ethods 

which can be performed entirely in the human mind are 

unpatentable not because there is anything wrong with 

claiming mental method steps as part of a process containing non-mental steps, but rather because computational methods which can be performed entirely in the 

human mind are the types of methods that embody the 

‘basic tools of scientific and technological work’ that are 

free to all men and reserved exclusively to none.” CyberSource Corp. v. Retail Decisions, Inc., 654 F.3d 1366, 1373 

(Fed. Cir. 2011) (citing Benson, 409 U.S. at 67); see also

Diamond v. Diehr, 450 U.S. 175, 187 (1981); SmartGene, 

Inc. v. Advanced Biological Labs., SA, 555 F. App’x 950, 

955 (Fed. Cir. 2014). 

Mayo itself considered and rejected diagnostic and 

therapeutic method claims that combined routine and 

conventional physical implementation of a law of nature

with a simple mental process step. An exemplary claim 

evaluated in Mayo recited “[a] method of optimizing 

therapeutic efficacy for treatment of [a] gastrointestinal 

disorder, comprising: (a) administering a [thiopurine] 

drug . . . and (b) determining the level of [a metabolite] . . . wherein” a certain low metabolite level indicated 

a need to increase drug dosage and a certain high metabolite level indicated a need to decrease drug dosage. Mayo, 

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132 S. Ct. at 1295. Mayo held that the “‘wherein’ clauses 

simply tell a doctor about the relevant natural laws, at 

most adding a suggestion that he should take those laws 

into account when treating his patient.” Id. at 1297. 

That is, “these clauses tell the relevant audience about 

the laws while trusting them to use those laws appropriately where they are relevant to their decisionmaking 

(rather like Einstein telling linear accelerator operators 

about his basic law and then trusting them to use it 

where relevant).” Id. 

Here, the phrase “to detect the allele” in claim 1 of the 

’179 patent also merely informs the relevant audience—

e.g., doctors or others seeking to make a genetic diagnosis—to apply a law of nature for a purpose—detecting a 

polymorphism within a coding region of an allele of interest. The limitation “to detect the allele” merely asks the 

user to compare the non-coding sequence he has amplified 

and analyzed with a library of non-coding sequences 

known to be in linkage disequilibrium with certain coding 

region alleles. This instruction to undertake a simple 

comparison step does not represent an unconventional, 

inventive application sufficient to make the claim patenteligible. “[T]o transform an unpatentable law of nature 

into a patent-eligible application of such a law, one must 

do more than simply state the law of nature while adding 

the words ‘apply it.’” Mayo, 132 S. Ct. at 1294 (citing 

Benson, 409 U.S. at 71–72). 

Ariosa is again relevant. The claims challenged and 

invalidated in Ariosa included claims 21 and 25 of U.S. 

Patent No. 6,258,540, methods of “performing a prenatal 

diagnosis.” Ariosa, 788 F.3d at 1374. To various routine 

and conventional steps of physical implementation (amplifying DNA in a blood sample and then performing 

analysis of that DNA to detect DNA of a particular 

origin), these claims also added a mental process step 

(performing a prenatal diagnosis based on the DNA 

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18 GENETIC TECHNOLOGIES LIMITED v. MERIAL L.L.C. 

detected). The mental process of “performing a prenatal 

diagnosis” based on the DNA detected is directly comparable to claim 1’s mental process of detecting the allele. 

The addition of this mental process step to the routine 

and conventional physical activity of amplification and 

analysis of DNA did not distinguish claims 21 and 25, 

which were invalidated with the other claims of the ’540 

patent. Ariosa, 788 F.3d at 1378. 

Our decision in In re BRCA1- & BRCA2-Based Hereditary Cancer Test, 774 F.3d 755 (Fed. Cir. 2014), is also 

instructive. Claim 8 of U.S. Patent No. 5,753,441 evaluated in that case recited a method of screening for alterations of the BRCA1 gene that included the steps of 

“amplifying all or part of a BRCA1 gene from [a] sample 

using a set of primers to produce amplified nucleic acids 

and sequencing the amplified nucleic acids” and “comparing” the sequence with wild-type BRCA1. Id. at 761–62. 

We held that claim to be invalid because it was directed to 

an abstract idea and did not add enough to distinguish it 

from a claim to the abstract idea. Id. at 762–65. An 

aspect of our analysis there supports our analysis of the 

law-of-nature issue here. We noted that “[t]he nonpatent-ineligible elements of claim[] . . . 8 do not add 

‘enough’ to make the claim[] as a whole patenteligible. . . . The [physical implementation steps] of 

claim[] . . . 8 do nothing more than spell out what practitioners already knew—how to compare gene sequences 

using routine, ordinary techniques.” Id. at 764. Claim 8, 

which combined conventional physical implementation of 

a law of genetics with a simple mental process step of 

“comparing,” was held to be patent-ineligible. Id. at 765. 

To be sure, it seems to be true, as GTG alleges, that at 

the time the ’179 patent was filed, no one was “using the 

non-coding sequence as a surrogate marker for the coding 

region allele.” Appellant’s Reply Br. at 7. Claim 1 was 

found by the patent examiner to be novel over the prior 

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art and survived multiple rounds of reexamination. But 

the novelty of looking to non-coding DNA to detect a 

coding region allele of interest resides in the novelty of 

the newly discovered natural law of linkage disequilibrium between coding and non-coding regions and adds little 

more than a restatement of the natural law itself. We 

thus hold that the simple mental process step of “detect[ing] the allele” in claim 1, either alone or in combination with the physical steps described above, does not 

supply sufficient inventive concept to make the claim 

patent-eligible under § 101. 

As a final matter, we note that GTG’s attempts to distinguish this case on the ground that the method of claim 

1 is useful have no basis in case law or in logic. Claim 1 

stands rejected under § 101 as ineligible for claiming 

unpatentable subject matter, not for lack of utility. The 

method claims of Mayo and Ariosa were apparently also 

useful, and also invalid. Mayo, 132 S. Ct. at 1294 (“[This 

case] concerns patent claims covering processes that help 

doctors who use thiopurine drugs to treat patients with 

autoimmune diseases determine whether a given dosage 

level is too low or too high.”); Ariosa, 788 F.3d at 1380 

(“We do not disagree that detecting cffDNA in maternal 

plasma or serum that before was discarded as waste 

material is a positive and valuable contribution to science. 

But even such valuable contributions can fall short of 

statutory patentable subject matter, as it does here.”) 

Utility is not the test for patent-eligible subject matter. 

See Bilski, 561 U.S. at 659 (Breyer, J., concurring). 

CONCLUSION

For the foregoing reasons, we hold that claim 1 of the 

’179 is invalid under 35 U.S.C. § 101 as directed to patentineligible subject matter. We therefore affirm the district 

court’s grant of appellees’ motions to dismiss under Rule 

12(b)(6).

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20 GENETIC TECHNOLOGIES LIMITED v. MERIAL L.L.C. 

AFFIRMED

COSTS

Costs to appellees. 

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