Appeals from the United States District Court for the
District of Delaware in Nos. 1:12-cv-00396-LPS,
1:12-cv-00394-LPS Chief Judge Leonard P. Stark.
B. LIEB, Sheridan Ross, PC, Denver, CO, argued for
plaintiff-appellant. Also represented by ROBERT R. BRUNELLI,
HIWOT M. COVELL.
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.
WIGMORE, Wilmer Cutler Pickering Hale and Dorr LLP,
Washington, DC, argued for defendant-appellee Bristol-Myers
Squibb Company. Also represented by THOMAS SAUNDERS, TRACEY
COTE ALLEN; WILLIAM F. LEE, ALLISON TRZOP, Boston, MA.
PROST, Chief Judge, DYK, and TARANTO, Circuit Judges.
118U.S.P.Q.2D 1542] Dyk, Circuit Judge.
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.
'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 defining 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
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.
1980s, Dr. Malcolm J. Simons, the named inventor of the
'179 patent, working with GTG, 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 historically, they appeared to
serve no function. '179 patent col. 5 ll. 42-46.
118U.S.P.Q.2D 1543] Dr. Simons found that the correlated
coding and non-coding 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
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
b) analyzing the amplified DNA sequence to detect the allele.
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 non-coding region, which
could be found within the same gene as the coding region,
within a different gene, or within an intergenic region.
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 non-coding 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.
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)" ...