BIO and AUTM File Joint Brief Defending Patentability of DNA-Based Inventions

No. 2010-1406
UNITED STATES COURT OF APPEALS FOR THE FEDERAL CIRCUIT
———————————
THE ASSOCIATION FOR MOLECULAR PATHOLOGY, THE AMERICAN
COLLEGE OF MEDICAL GENETICS, THE AMERICAN SOCIETY FOR
CLINICAL PATHOLOGY, THE COLLEGE OF AMERICAN PATHOLOGISTS,
HAIG KAZAZIAN, MD, ARUPA GANGULY, PhD, WENDY CHUNG, MD,
PhD, HARRY OSTRER, MD, DAVID LEDBETTER, PhD, STEPHEN
WARREN, PhD, ELLEN MATLOFF, M.S., ELSA REICH, M.S., BREAST
CANCER ACTION, BOSTON WOMEN’S HEALTH BOOK COLLECTIVE,
LISBETH CERIANI, RUNI LIMARY, GENAE GIRARD, PATRICE FORTUNE,

VICKY THOMASON, and KATHLEEN RAKER,
Plaintiffs-Appellees,
v.
UNITED STATES PATENT AND TRADEMARK OFFICE,
Defendant,
and
MYRIAD GENETICS, INC.,
Defendant-Appellant,
and
LORRIS BETZ, ROGER BOYER, JACK BRITTAIN, ARNOLD B. COMBE,
RAYMOND GESTELAND, JAMES U. JENSEN, JOHN KENDALL MORRIS,
THOMAS PARKS, DAVID W. PERSHING, and MICHAEL K. YOUNG, in their
official capacity as Directors of the University of Utah Research Foundation,
Defendants-Appellants,
———————————
Appeal from the United States District Court for the Southern District of New
York in Case No. 09-CV-4515, Senior Judge Robert W. Sweet
———————————
BRIEF FOR THE BIOTECHNOLOGY INDUSTRY ORGANIZATION AND
THE ASSOCIATION OF UNIVERSITY TECHNOLOGYMANAGERS
AS AMICI CURIAE SUPPORTING REVERSAL
———————————
MARK C. FLEMING
ALLEN C. NUNNALLY
WILMER CUTLER PICKERING
HALE AND DORR LLP
SETH P.WAXMAN
THOMAS G. SAUNDERS
WILMER CUTLER PICKERING
HALE AND DORR LLP
(Full Counsel Information on Reverse)
MARK C. FLEMING
ALLEN C. NUNNALLY
WILMER CUTLER PICKERING
HALE AND DORR LLP
60 State Street
Boston, MA 02109
(617) 526-6000
SETH P.WAXMAN
THOMAS G. SAUNDERS
WILMER CUTLER PICKERING
HALE AND DORR LLP
1875 Pennsylvania Avenue, NW
Washington, DC 20006
(202) 663-6000
Of Counsel:
HANS SAUER
BIOTECHNOLOGY INDUSTRY ORGANIZATION
1201 Maryland Avenue, SW, Suite 900
Washington, DC 20024
(202) 962-6695

ii
TABLE OF CONTENTS
Page
CERTIFICATE OF INTEREST................................................................................ i
TABLE OF AUTHORITIES ................................................................................... iii
STATEMENT OF INTEREST..................................................................................1
INTRODUCTION .....................................................................................................3
ARGUMENT.............................................................................................................4
I. ISOLATED DNAMOLECULES ARE PATENTABLE SUBJECT MATTER .................4
A. Isolated DNA Molecules Are New Man-Made Compositions
Of Matter ...............................................................................................5
B. Isolated DNA Molecules Are Chemical Compounds With
New And Distinctive Properties And Uses Compared To
Naturally-Occurring DNA...................................................................12
C. The District Court Improperly Treated DNA Molecules As
“Different” From Every Other Chemical Compound,
Incorrectly Treating DNA As Mere Information ................................18
II. INVALIDATING PATENTS ON ISOLATED DNAMOLECULES WOULD
DISCOURAGE, NOT PROMOTE, INNOVATION ...................................................20
A. Patents On Isolated DNA Molecules Promote Innovation .................20
B. A Decision That Isolated DNA Molecules Are Not Patent-
Eligible Would Have Far-Reaching Negative Consequences.............24
III. CLAIMS TO ISOLATED DNAMOLECULES DO NOT HARM PATIENTS
OR IMPEDE THE PROGRESS OF SCIENCE .........................................................27
A. Patents On Isolated DNA Molecules Benefit Rather Than
Harm The Public .................................................................................28
B. Patents On Isolated DNA Molecules Do Not Impede The
Progress Of Science.............................................................................29
CONCLUSION........................................................................................................33
CERTIFICATES OF SERVICE AND COMPLIANCE
iii
TABLE OF AUTHORITIES
CASES
Page(s)
American Fruit Growers, Inc. v. Brogdex Co.,
283 U.S. 1 (1931).....................................................................................14, 17
American Wood-Paper Co. v. Fiber Disintegrating Co.,
90 U.S. (23 Wall.) 566 (1874) .......................................................................10
Amgen, Inc. v. Chugai Pharmaceutical Co.,
927 F.2d 1200 (Fed. Cir. 1991) ...............................................................12, 20
Bilski v. Kappos,
130 S. Ct. 3218 (2010)...................................................................................11
Cochrane v. Badische Anilin & Soda Fabrik,
111 U.S. 293 (1884).................................................................................10, 11
Diamond v. Chakrabarty,
447 U.S. 303 (1980).........................................................................3, 5, 12, 15
Eli Lilly & Co. v. Premo Pharmaceutical Laboratories, Inc.,
630 F.2d 120 (3d Cir. 1980) ..........................................................................29
Farbenfabriken of Elberfeld Co. v. Kuehmsted,
171 F. 887 (C.C.N.D. Ill. 1909)...............................................................13, 16
Fiers v. Revel,
984 F.2d 1164 (Fed. Cir. 1993) .....................................................................12
Funk Bros. Seed Co. v. Kalo Inoculant Co.,
333 U.S. 127 (1948).................................................................................16, 17
Hartranft v. Wiegmann,
121 U.S. 609 (1887)...........................................................................14, 15, 17
In re Deuel,
51 F.3d 1552 (Fed. Cir. 1995) .......................................................................12
In re Fisher,
421 F.3d 1365 (Fed. Cir. 2005) .....................................................................11
iv
In re Gleave,
560 F.3d 1331 (Fed. Cir. 2009) .....................................................................11
In re Kubin,
561 F.3d 1351 (Fed. Cir. 2009) .....................................................................11
In re Merz,
97 F.2d 599 (C.C.P.A. 1938).........................................................................15
Merck & Co. v. Olin Mathieson Chemical Corp.,
253 F.2d 156 (4th Cir. 1958) .........................................................................15
Merck KGaA v. Integra Lifesciences I, Ltd.,
545 U.S. 193 (2005).......................................................................................32
Parke-Davis & Co. v. H.K. Mulford Co.,
189 F. 95 (C.C.S.D.N.Y. 1911) .....................................................................14
Regents of University of California v. Eli Lilly & Co.,
119 F.3d 1559 (Fed. Cir. 1997) .....................................................................11
Scripps Clinic & Research Foundation v. Genentech, Inc.,
666 F. Supp. 1379 (N.D. Cal. 1987)..............................................................15
Whittemore v. Cutter,
29 F. Cas. 1120 (C.C.D. Mass. 1813) (No. 17,600)......................................32
STATUTES AND REGULATIONS
35 U.S.C.
§ 101 ............................................................................................................3, 4
§ 102 ..............................................................................................................11
§ 103 ..............................................................................................................11
§ 112 ..............................................................................................................11
§ 271(e)(1) .....................................................................................................32
USPTO Utility Examination Guidelines, 66 Fed. Reg. 1092 (2001) ................10, 13
v
OTHER AUTHORITIES
Adelman, David E. & Kathryn L. DeAngelis, Patent Metrics, 85 Tex.
L. Rev. 1677 (2007).......................................................................................30
Alter, Harvey J. & Michael Houghton, Hepatitis C Virus and
Eliminating Post-Transfusion Hepatitis, 6 Nature Medicine
1082 (2000)....................................................................................................21
AUTM, University Technology Transfer, http://www.autm.net/AM/
Template.cfm?Section=White_Papers&Template=/CM/Content
Display.cfm&ContentID=1895 .....................................................................26
Barfield, Claude & John E. Calfee, Biotechnology and the Patent
System (2007).................................................................................................26
Biotechnology Industry Organization, Guide to Biotechnology
(2008), available at http://www.bio.org/speeches/pubs/er/
BiotechGuide2008.pdf.................................................... 21, 22, 23, 24, 25, 26
Boston Consulting Group, Rising to the Productivity Challenge
(2004).............................................................................................................29
Caulfield, Timothy, et al., Evidence and Anecdotes: An Analysis of
Human Gene Patenting Controversies, 24 Nature Biotech. 1091
(2006).............................................................................................................30
Chisum on Patents §1.02[3][a] (2010) ....................................................................14
Cideciyan, Arthur V., et al., Human Gene Therapy for RPE65
Isomerase Deficiency Activates the Retinoid Cycle of Vision But
With Slow Rod Kinetics, 105 Proc. Nat’l Acad. Sci. 15112
(2008).............................................................................................................22
Collins, Francis S., Personalized Medicine, Boston Globe, July 17,
2005, at E12...................................................................................................23
Davies, Kevin, Cracking the Genome (2001)..........................................................27
Ernst & Young, Beyond Borders: Global Biotechnology Report
(2009).............................................................................................................25
vi
Federal Trade Commission, Emerging Healthcare Issues (2009) ..........................28
GeneTests, Growth of Laboratory Directory (2010), http://www.ncbi.
nlm.nih.gov/projects/GeneTests/static/whatsnew/labdirgrowth.
shtml...............................................................................................................23
Grabowski, Henry, et al., The Market for Follow-On Biologics,
25 Health Affairs 1291 (2006).......................................................................26
Grabowski, Follow-On Biologics, 7 Nature Reviews Drug Discovery
479, 482 (2008)..............................................................................................25
Holman, Christopher M., The Impact of Human Gene Patents on
Innovation and Access, 76 UMKC L. Rev. 295 (2007) ................................32
Huys, Isabelle, et al., Legal Uncertainty in the Area of Genetic
Diagnostic Testing, 27 Nature Biotech. 903 (2009)......................................32
Jelkmann, Wolfgang, Molecular Biology of Erythropoietin,
43 Internal Medicine 649 (2004)...................................................................20
National Human Genome Research Institute, Chromosome,
http://www.accessexcellence.org/RC/VL/GG/nhgri_PDFs/
chromosome.pdf ..............................................................................................7
National Research Council, Reaping the Benefits of Genomic and
Proteomic Research (2006) ...........................................................................31
Property Rights: The Granting of Patents on Human Genes Has So
Far Not Been the Disaster It Was Predicted To Be, 458 Nature
386 (2009)......................................................................................................28
U.S. National Library of Medicine, Chromosome 17,
http://ghr.nlm.nih.gov/chromosome/17 .......................................................7, 8
U.S. National Library of Medicine, BRCA1,
http://ghr.nlm.nih.gov/gene/BRCA1 ...............................................................8
Walsh, John P., et al., View from the Bench, 309 Science 2002 (2005)..................31
vii
Walsh, John P., et al., Patents, Material Transfers and Access to
Research Inputs in Biomedical Research (Sept. 20, 2005),
available at http://www2.druid.dk/conferences/viewpaper
.php?id=776&cf=8...................................................................................31, 32
Walsh, John P., et al., Working Through the Patent Problem,
299 Science 1021 (2003) ...............................................................................31
Watson, James D., et al., Molecular Biology of the Gene (6th ed.
2008) ........................................................................................................6, 7, 8
1
STATEMENT OF INTEREST
The Biotechnology Industry Organization (“BIO”) is the country’s largest
biotechnology trade association, representing over 1100 companies, academic
institutions, and biotechnology centers in all 50 States and countries around the
world. BIO members undertake research and development of biotechnological
healthcare, agricultural, environmental, and industrial products. BIO members
range from start-up businesses and university spin-offs to Fortune 500
corporations. The vast majority of BIO’s members are small companies that have
yet to bring products to market or attain profitability, and thus rely heavily on
venture capital and other private investment. Patents on isolated DNA molecules
are frequently critical to a biotech company’s ability to attract the investment
necessary for development of innovative therapeutic, diagnostic, environmental,
renewable energy, and agricultural products.

The Association of University Technology Managers (“AUTM”) is the
largest association of university technology transfer professionals, with members
from over 350 universities, research institutions, teaching hospitals, and
government agencies worldwide, as well as hundreds of companies involved with
managing and licensing innovations derived from academic and nonprofit research.
The issues raised in this case are of great importance to BIO’s and AUTM’s
members. BIO and AUTM have no commercial interest in the parties to this
action. None of the parties nor the University of Utah Research Foundation is a
member of BIO or AUTM.

All parties have consented to the filing of this brief.

INTRODUCTION
“[C]ourts should not read into the patent laws limitations and conditions
which the legislature has not expressed.” Diamond v. Chakrabarty, 447 U.S. 303,
308-309 (1980) (internal quotation marks omitted). The district court regrettably
did just that, ignoring Congress’s intent that statutory subject matter under Section
101 expansively include all products of human ingenuity. Id. at 309-310.
Isolated DNA molecules are unquestionably “composition[s] of matter,” 35
U.S.C. §101; the district court’s ruling that they are nonetheless categorically
unpatentable rested on three fundamental errors.1 First, the court incorrectly
treated isolated DNA molecules as merely “purified” forms of naturally-occurring
substances; in fact, they are new, man-made chemical compositions that do not
occur in nature. Second, even if isolated DNA molecules could be treated as
purified versions of naturally-occurring DNA, the process of isolation requires
such a level of human intervention and so alters their character and use as to make
them patentable under settled law. Third, the district court was led astray by the
comparison of DNA sequences to “information”—a common metaphor that is
useful in conveying complex science to laypersons, but that does not change the
fact that DNA remains a chemical compound, not an alphabet or a language. The
utility of isolated DNA molecules derives from their chemical structure, which is,
and can only be, developed by human ingenuity using complex scientific expertise
and equipment. As a result, isolated DNA molecules are patentable subject matter.
Unless reversed, the district court’s ruling will seriously harm the U.S.
biotechnology industry, which consists largely of small firms that are engaged in
foundational research and dependent on private investment, not product revenues,
to fund their work. Patent protection is essential to the ability of biotechnology
firms to secure such private investment. If this Court affirms the district court’s
categorical rejection of the patentability of isolated DNA molecules, it would cast a
cloud of uncertainty over thousands of similar patents and compromise the ability
of biotechnology firms to pursue groundbreaking discoveries in human healthcare,
renewable energy, and sustainable agriculture; it would also harm university
research and innovation by impeding the transfer of technology from the academy
to industry. Conversely, there is no basis for Plaintiffs’ contention that patenting
isolated DNA molecules stifles scientific innovation. Numerous recent studies
confirm that such patents have not interfered with scientific progress; on the
contrary, they safeguard and encourage innovation by ensuring that U.S. research
entities can obtain the necessary capital to perform critical biotechnology research.

ARGUMENT

I. ISOLATED DNAMOLECULES ARE PATENTABLE SUBJECT MATTER
Congress has framed patent eligibility broadly, to include “any new and
useful … composition of matter.” 35 U.S.C. §101. Although isolated DNA
molecules clearly are “composition[s] of matter,” the district court ruled them
unpatentable because it believed them to be the “purification of a product of
nature” and patentable only if they possessed “markedly different characteristics”
from naturally-occurring DNA. A214 (quoting Chakrabarty, 447 U.S. at 310).
The district court’s analysis was doubly flawed. First, isolated DNA
molecules are not the “purification” of naturally-occurring DNA. Rather, they are
entirely different man-made molecules that do not appear in nature. Second, even
if isolated DNA molecules could be considered “purified” forms of native DNA,
the isolation process transforms the DNA into a new and different article with
distinctive form, properties, and uses, rendering the isolated molecules patentable
under longstanding precedent.

A. Isolated DNA Molecules Are New Man-Made Compositions Of
Matter
The district court appeared to assume, without explanation, that isolated
DNA molecules are merely the “purification” of naturally-occurring substances,
rather than new substances all their own. A214. That was error. Isolated DNA
molecules are freestanding chemical compounds that do not occur in nature, but
rather are created by human ingenuity and, accordingly, are patentable.
Human DNA in its natural or “native” form exists as part of structures called
chromosomes within the nucleus of human cells. Chromosomes are complex,
stable structures consisting of extremely long strands of DNA bound together with
numerous proteins (such as histones), which give the chromosome compact form,
regulate the functions of DNA, and account for half the molecular mass of the
chromosome. Watson et al., Molecular Biology of the Gene 135 (6th ed. 2008)
(“Watson”). DNA is composed of double-stranded chains of smaller components
known as “nucleotides,” which form complementary “base pairs” in DNA’s
double-helical structure. A125-126. Shorter sequences of nucleotides within each
chromosome form functional units called “genes.” A121.

National Human Genome Research Institute, Chromosome, http://www.access
excellence.org/RC/VL/GG/nhgri_PDFs/chromosome.pdf. Through a series of
complex chemical interactions with enzymes in the body, genes participate in
production of proteins that serve various biological functions. Watson 377-383,
457-458. Genes, however, contain some nucleotide stretches known as “introns”
that do not contribute to protein production; nucleotide stretches that do contribute
to protein production are called “exons.” A121-122.
Critically, at no point in the process of protein production—or at any other
point in an organism’s natural life—are genes excised or uncoupled from the rest
of the chromosome. That is, genes do not naturally exist as stand-alone molecules
or separate chemical compounds.

Isolated DNA molecules differ significantly from naturally-occurring,
chromosomal DNA. Isolated DNA molecules are much smaller than chromosomal
DNA, frequently corresponding only to a single gene. For example, the BRCA1
gene in its native form appears on human chromosome 17, which itself contains
about 80 million base pairs. U.S. National Library of Medicine, Chromosome 17,
2 All Internet sites were last visited on October 29, 2010.
3 The district court noted that certain chromosomal DNA can dissociate from
certain proteins during particular cellular processes. A128. That does not mean,
however, that genes exist separately from the much larger chromosomes. Rather,
native DNA remains fixed in its chromosomal context and does not become a
freestanding molecule. See Watson 135-36, 159.
http://ghr.nlm.nih.gov/chromosome/17 (“Chromosome 17”). An isolated molecule
of the BRCA1 gene, however, consists of only about 80,000 nucleotide pairs (see
id., BRCA1, http://ghr.nlm.nih.gov/gene/BRCA1) and exists and is usable outside
of human cells (A588-619). Creation of an isolated BRCA1 DNA molecule
requires identification of the gene among more than 20,000 genes that comprise the
human genome and the 1200-1500 genes on the vast length of chromosome 17.
Chromosome 17. The desired portion of chromosomal DNA is then excised from
the rest of the chromosome by unbundling the chromosomal DNA from structural
proteins and breaking particular covalent chemical bonds in the sugar-phosphate
backbone of the chromosomal DNA. A127. The excised DNA molecule must
typically be “amplified” (replicated million-fold through laboratory techniques to
generate sufficient DNA for automated sequencing) and physically separated from
other genomic DNA through a technique such as gel electrophoresis. See Watson
740-741, 751-757. This process yields a new and separate chemical compound
that does not exist in nature.

The distinction between native chromosomal DNA and the artificial
chemical compounds at issue is even starker in the case of so-called
complementary DNA, or “cDNA.” cDNA molecules consist solely of exons,
nucleotide stretches that contribute directly to the production of proteins. A133-
134. cDNA does not occur naturally in the body; indeed, even the nucleotide
sequence of a cDNA molecule has no analogue in native chromosomal DNA,
where the nucleotide sequences are interrupted by introns. A134. For example,
the naturally-occurring BRCA1 and 2 genes each contain more than 70,000
nucleotides, while the exons that make up their corresponding cDNA molecules
together have fewer than 16,000. A3656-3657. Thus, the structure of the claimed
isolated cDNA molecules differs substantially from that of the natural BRCA
genes.
The district court notably did not rule that isolated genomic DNA molecules
or cDNA were naturally-occurring substances. Rather, it framed the question as
“whether or not claims directed to isolated DNA containing naturally-occurring
sequences fall within the products of nature exception.” A195-196. Even leaving
aside the dubious legal status of a “product[] of nature exception” as the court
conceived it (cf. Appellants’ Br. 35, 41), the court erroneously compared the
claimed molecules to naturally-occurring nucleotide sequences, rather than to
naturally-occurring DNA molecules. Although they share the nucleotide sequence
4 The district court appeared to suggest that naturally-occurring
“pseudogenes” within an organism’s chromosomal DNA necessarily contain
identical nucleotide sequences to cDNA molecules corresponding to genes. A134,
A222. The evidence the district court cited does not support that conclusion. One
witness testified that nucleotide sequences in pseudogenes differed from cDNA
sequences by at least 10%. A6974-6975. Another referenced an example where
only a portion of BRCA1 cDNA was contained in the chromosomal DNA as a
pseudogene. A7023. And in both examples, the pseudogene sequences—unlike
cDNA—remain fixed portions of the larger chromosomal sequence, not
freestanding molecules.of some portion of chromosomal DNA, isolated genomic DNA molecules do not occur naturally because they are new and distinct molecules with different
chemical structures from naturally-occurring DNA in a chromosome. The same is
true a fortiori of cDNA, which does not even contain the same nucleotide sequence
as any naturally-occurring gene in a chromosome. The USPTO has acknowledged
the patentability of isolated DNA molecules for precisely these reasons. USPTO
Utility Examination Guidelines, 66 Fed. Reg. 1092, 1093 (2001) (“An isolated and
purified DNA molecule that has the same sequence as a naturally occurring 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 .… Like
other chemical compounds, DNA molecules are eligible for patents when isolated
from their natural state and purified[.]” (emphasis added)).

The district court also erroneously relied on two early Supreme Court cases
that invalidated patents for lack of novelty because the claimed substances
previously existed. A203-204. In American Wood-Paper Co. v. Fiber
Disintegrating Co., the Court ruled that a patent on wood pulp was “void for want
of novelty” because “whatever may be said of their process for obtaining it, the
product was in no sense new.” 90 U.S. (23 Wall.) 566, 595 (1874). Likewise, in
Cochrane v. Badische Anilin & Soda Fabrik, the Court found a patent on “artificial
alizarine” invalid because alizarine was not a “new composition of matter” but an
“old article.” 111 U.S. 293, 311 (1884). Neither opinion suggested, however, that
a man-made molecule that did not previously exist was unpatentable subject
matter.

Of course, the mere fact that isolated DNA molecules are patentable subject
matter does not mean that every such molecule can be validly patented. Rather,
patent eligibility is “only a threshold test”; a claimed invention must also be
“novel, see §102, nonobvious, see §103, and fully and particularly described, see
§112.” Bilski v. Kappos, 130 S. Ct. 3218, 3225 (2010). Accordingly, this Court
has rejected claims to isolated DNA molecules on grounds of anticipation,
obviousness, lack of utility, and failure to comply with the requirements of 35
U.S.C. §112. E.g., In re Gleave, 560 F.3d 1331 (Fed. Cir. 2009) (patent to
antisense DNA sequences denied as anticipated in light of prior art); In re Kubin,
561 F.3d 1351 (Fed. Cir. 2009) (affirming USPTO’s obviousness rejection of a
patent on a DNA molecule); Regents of Univ. of Cal. v. Eli Lilly & Co., 119 F.3d
1559 (Fed. Cir. 1997) (claim to a vertebrate cDNA sequence encoding insulin held
invalid for lack of written description); In re Fisher, 421 F.3d 1365 (Fed. Cir.
2005) (rejecting claims to expressed sequence tags—short DNA molecules of
unspecified cellular function—for lack of sufficient utility). None of these cases
suggested that isolated DNA molecules were categorically unpatentable. Indeed,
this Court has frequently upheld patents to isolated DNA molecules without
suggesting that the subject matter raised concerns under Section 101.5
Accordingly, the district court erred in assuming that isolated DNA
molecules and cDNA are merely “purification[s]” of naturally-occurring
substances. Rather, they are new compositions of matter that exist only when
created by human ingenuity. That suffices to meet Section 101’s requirement of
patentable subject matter. See Chakrabarty, 447 U.S. at 309 (upholding
patentability of genetically-engineered bacterium that was a “nonnaturally
occurring manufacture or composition of matter”).

B. Isolated DNA Molecules Are Chemical Compounds With New
And Distinctive Properties And Uses Compared To Naturally-
Occurring DNA
Even if the district court had been correct to treat isolated DNA molecules as
purified products of nature, rather than as the new and distinct chemical
compositions that they are, this Court should still reverse because isolated genomic
DNA and cDNA molecules are man-made and exhibit new and distinctive
“character” and “uses” compared to native DNA. Indeed, as discussed more fully
in Part II below, the U.S. biotechnology industry was launched largely because of
the possibility of using isolated DNA molecules for important medical applications
5 E.g., In re Deuel, 51 F.3d 1552, 1560 (Fed. Cir. 1995); Amgen, Inc. v.
Chugai Pharm. Co., 927 F.2d 1200, 1206 (Fed. Cir. 1991); Fiers v. Revel, 984
F.2d 1164 (Fed. Cir. 1993).
such as gene therapy and manufacture of therapeutic proteins, for which naturallyoccurring
DNA is useless. Thus, even accepting the district court’s incorrect
assumption that isolated DNA molecules are the “purification” of naturallyoccurring
substances, they are still patentable subject matter under governing
precedent.

The United States has a long history of issuing patents covering purified
substances (including substances derived from plants and other organic extracts)
that acquire new and distinctive characteristics and properties through human
ingenuity. In 1873, Louis Pasteur received U.S. Patent 141,072, which claimed
“[y]east, free from organic germs of disease, as an article of manufacture.” See
USPTO Utility Examination Guidelines, 66 Fed. Reg. at 1093. A patent issued in
1900 claimed purified acetylsalicylic acid (aspirin), a naturally-occurring substance
previously obtained only in impure form as a “product of coal tar.”

Farbenfabriken of Elberfeld Co. v. Kuehmsted, 171 F. 887, 890 (C.C.N.D. Ill.
1909) (upholding patent against invalidity challenge, noting that the inventor “took
a comparatively worthless substance and changed it into a valuable one”). And in
1911, Judge Learned Hand, sitting as a district judge, ruled that the utility of
purified adrenaline extracted from animal glands rendered it patentable:
[E]ven if it were merely an extracted product without change, there is
no rule that such products are not patentable. [The inventor] was the
first to make it available for any use by removing it from the other
gland-tissue in which it was found, and, while it is of course possible
logically to call this a purification of the principle, it became for every
practical purpose a new thing commercially and therapeutically. That
was a good ground for a patent.

Parke-Davis & Co. v. H.K. Mulford Co., 189 F. 95, 103 (C.C.S.D.N.Y. 1911),
aff’d in relevant part, 196 F. 496 (2d Cir. 1912).6
The Supreme Court has similarly indicated that a preexisting product
(whether sourced naturally or otherwise) that undergoes a “transformation”
producing a “new and different article” with “‘a distinctive name, character, or
use’” is a patentable “manufacture.” American Fruit Growers, Inc. v. Brogdex
Co., 283 U.S. 1, 12-13 (1931) (quoting Hartranft v. Wiegmann, 121 U.S. 609, 613,
615 (1887)) (ruling a borax-coated orange patent-ineligible because it “remains a
fresh orange, fit only for the same beneficial uses as theretofore”).7 Other courts
considering whether purified substances were patentable over preexisting impure
extracts have likewise pointed to new and beneficial uses of the claimed invention
6 Contrary to the district court’s reasoning (A209-210), Judge Hand’s
observation that a purification that produces “a new thing” with a new use renders
the resulting product patent-eligible is consistent with the Supreme Court’s
decisions, as discussed below.

7 It is far from clear that American Fruit Growers imposed a general rule of
patentability, as opposed to a characteristic of a “manufacture,” and the decision
has been criticized even on its own terms. See, e.g., Chisum on Patents §1.02[3][a]
(2010) (noting that a borax-coated orange that proved mold resistant would have a
distinctive quality or property). Nonetheless, even assuming that Section 101
requires that a patentable product have a “new or distinctive form, quality or
property” compared to a naturally-occurring item, the isolated DNA molecules at
issue here plainly satisfy that test. as the defining criterion. E.g., In re Merz, 97 F.2d 599, 601 (C.C.P.A. 1938) (“[I]f the process produces an article of such purity that it differs not only in degree but in kind[,] it may be patentable. If it differs in kind, it may have a new utility in
which invention may rest.”); see also Merck & Co. v. Olin Mathieson Chem.
Corp., 253 F.2d 156, 164-165 (4th Cir. 1958) (upholding claims to vitamin B12
compositions because, even if viewed as “purification of the active principle in
natural fermentates,” the claimed compositions possessed significant utility
compared to the “quite useless” natural fermentates, such that the “new products
are not the same as the old”); Scripps Clinic & Research Found. v. Genentech,
Inc., 666 F. Supp. 1379, 1389 n.6 (N.D. Cal. 1987) (noting that purified Factor
VIII:C, a natural blood clotting protein, is patent-eligible).

Isolated DNA and cDNA molecules have a significantly different
“character” and “use” compared to genes within their native setting, i.e., within a
large and complex chromosomal DNA molecule. In their natural form, human
genes are trapped in the midst of other chromosomes and all the hundreds of other
8 Contrary to the district court’s apparent belief (A212 n.48), Chakrabarty
did not adopt an additional requirement that a claimed purified substance have
“markedly different characteristics” from the natural substance. The Court’s
observation that the claimed strain of bacteria had “markedly different
characteristics from any found in nature and one having the potential for
significant utility,” Chakrabarty, 447 U.S. at 311, merely confirmed that the
claimed strain had a “distinctive name, character, or use,” Hartranft, 121 U.S. at
615 (cited in Chakrabarty, 447 U.S. at 309-310). In any event, as shown in text,
isolated DNA molecules do possess “markedly different characteristics” from
naturally-occurring chromosomal DNA components of a cell; they are essentially inaccessible and under the control of the physiology of the organism in which they reside. A125-126. Native DNA serves its natural purpose within a cell, but it cannot be used in virtually any practical
diagnostic, therapeutic, or industrial application. In this respect, it resembles the
therapeutically useless “product of coal tar.” Farbenfabriken, 171 F. at 887.
Isolating a DNA molecule, in addition to creating a whole new chemical
composition that does not exist in nature (see supra §I.A), imparts new utilities and
functions unavailable from native DNA. For example, one of the patents-in-suit
contemplates gene therapy using isolated DNA molecules that can be copied many
times over and then introduced into patients’ cells to replace missing, mutated,
cancer-inducing, or otherwise malfunctioning genes. A603 (32:34-33:20).
Isolated DNA molecules can also be introduced into bacterial, yeast, or
mammalian host cell expression systems to produce proteins (such as tumor
suppressing proteins) in mass quantities and with a quality that natural sources
cannot produce, thereby permitting therapeutic uses. A604 (34:39-63).
Native DNA simply cannot be used in these therapeutic applications.
Rather, it is only when a new, isolated DNA molecule is produced independently
from a chromosome that these uses become possible. Accordingly, this is not a
situation in which natural substances “serve the ends nature originally provided
and act quite independently of any effort of the patentee.” Funk Bros. Seed Co. v.
Kalo Inoculant Co., 333 U.S. 127, 131 (1948). Rather, isolated DNA molecules
serve ends that nature never contemplated and that would be impossible without
the intervening effort of the patentee. They are accordingly “new and different
article[s]” that have distinctive “character” and “use” compared to native DNA.
American Fruit Growers, 283 U.S. at 12-13 (quoting Hartranft, 121 U.S. at 615).
The district court dismissed the utility of isolated DNA molecules as
“primarily a function of the nucleotide sequence identity between native and
isolated BRCA1/2 DNA.” A224 (emphasis added). But the utility of isolated
DNA is no more attributable to its similarity to native DNA than the utilities of
insulin, penicillin, vitamin B12, adrenaline, or other drug preparations are due to
their similarity to their naturally-occurring counterparts. The district court’s
observation could be made about essentially any biotechnology product. An
inquiry into why isolated DNA is useful, however, cannot detract from the fact that
it is useful. Its utility depends on the fact of isolation: the isolated molecule’s
chemical separation from other genomic material in the chromosome and its
resulting amenability to use as a therapeutic, diagnostic, or industrial tool. It is not
as though native DNA can be used in those applications or that isolated molecules
are effective to a greater degree; rather, native DNA cannot be used for such
purposes at all. That is the “character” and “use” that distinguishes isolated DNA
molecules from native DNA for purposes of patentability.

C. The District Court Improperly Treated DNA Molecules As
“Different” From Every Other Chemical Compound, Incorrectly
Treating DNA As Mere Information

The district court’s ruling also rested on its fundamentally erroneous
decision to ignore “the chemical nature of DNA” and instead treat DNA as “a
physical embodiment of information.” A217 (emphasis added). The court often
employed this metaphor, likening DNA’s nucleotide sequence to “information”—
whether in a chromosome within the human body or in isolated molecules in a
laboratory. E.g., A95-96 (“DNA represents the physical embodiment of biological
information, distinct in its essential characteristics from any other chemical found
in nature.”); A121 (each gene “contains the information used by the body to
produce those proteins”); A123 (“Gene sequences constitute biological information
insofar as they describe the structural and chemical properties of a particular DNA
molecule and serve as the cellular ‘blueprint’ for the production of proteins.”).
DNA sequences are often analogized to “information,” in that the sequence
of particular nucleotides in a gene can be said to “tell” which protein is produced.
But the various “informational” metaphors used in nomenclature for chemical
processes associated with DNA—transcription, translation, editing, codes—are just
that: metaphors. DNA itself is a chemical, and proteins are produced through
chemical reactions.9 The description of those reactions as a relaying of
“information” may be useful as a pedagogical tool, but it does not differentiate
DNA from any other chemical compound. In the presence of appropriate enzymes
and reactants, under appropriate conditions, DNA participates in a series of
chemical reactions that form proteins, just as other enzymatically-driven chemical
reactions take place to form various products.

To be sure, DNA plays an important role in biology. But the proposition
that native DNA has “unique properties … that distinguish it from all other
chemicals and biological molecules found in nature” (A216 n.51) is not a reason to
treat man-made, isolated DNA molecules differently under Section 101 from other
man-made chemical compounds. The statute does not justify a one-off exception
for isolated DNA molecules merely because DNA can be metaphorically described
as “information” (A136, A217), as “fundamental to biological thought” (A216), or
as our “common heritage” (A119). Isolated DNA and cDNA molecules are
chemical compounds. That they possess characteristics that can be compared to
information or language does not change their fundamental nature as
“compositions of matter” that are patentable under Section 101.

Specifically, enzymes interacting with a gene’s nucleotide sequence
catalyze the formation of mRNA, another type of molecule also comprised of
nucleotides but that excludes introns. Other enzymes, in turn, interact with the
mRNA molecules to catalyze the formation of strings of amino acids or
“polypeptides,” which eventually become the proteins that serve the body’s various
biological functions.

II. INVALIDATING PATENTS ON ISOLATED DNAMOLECULES WOULD
DISCOURAGE, NOT PROMOTE, INNOVATION
A. Patents On Isolated DNA Molecules Promote Innovation
Patents on isolated DNA molecules have featured prominently in a number
of biotechnology success stories. For example, Amgen’s pioneering work with
erythropoietin revolutionized the treatment of anemia. Patients with renal failure
frequently suffered from anemia due to insufficient erythropoietin; a full 25% of
renal patients on dialysis required regular blood transfusions before Amgen
isolated the DNA that codes for erythropoietin and made it therapeutically
available. Jelkmann, Molecular Biology of Erythropoietin, 43 Internal Medicine
649, 649 (2004). Amgen’s development and marketing of its therapeutic,
Epogen®, virtually eliminated the need for such transfusions. Amgen’s patent on
the isolated DNA molecule for erythropoietin, U.S. Patent No. 4,703,008, has been
critical in protecting this breakthrough. E.g., Amgen, Inc. v. Chugai Pharm. Co.,
927 F.2d 1200 (Fed. Cir. 1991).

Another prominent success story involves Chiron Corporation, which now
operates as Novartis Vaccines & Diagnostics. For decades, patients receiving
blood transfusions were at serious risk of contracting a deadly form of Hepatitis
formerly known as “Non-A, Non-B Hepatitis.” After nearly a decade of research,
Chiron scientists identified, isolated, characterized, and cloned the Hepatitis C
Virus (HCV) genome. Chiron’s patenting of certain isolated HCV DNA molecules
helped attract the investment and licensing revenue that allowed it to develop
screening methods that dramatically changed blood testing. Screening for HCV
nucleic acids using Chiron’s patented discoveries has reduced the incidence of
contracting Hepatitis C during a blood transfusion from an alarming 1:25 chance in
1989 to near zero today. Alter & Houghton, Hepatitis C Virus and Eliminating
Post-Transfusion Hepatitis, 6 Nature Medicine 1082, 1083 fig. 2 (2000).
Patents on isolated DNA molecules have been critical in developing other
important technologies:

Therapeutic Proteins. DNA-based therapeutics are used to treat many
diseases and conditions, including cancer, diabetes, growth deficiency, rheumatoid
arthritis, hemophilia, and hepatitis. Although recombinant DNA and cell cultures
are generally used to produce therapeutic replacement proteins and monoclonal
antibodies, patents on isolated DNA encourage foundational research and facilitate
the disclosure and additional investment needed to bring DNA-based therapeutics
to market.

Gene Therapy. Replacement gene therapy can treat diseases caused by the
lack of a particular protein, such as hemophilia or severe combined
immunodeficiency disease (SCID). BIO, Guide to Biotechnology 34 (2008),
available at http://www.bio.org/speeches/pubs/er/BiotechGuide2008.pdf (“Guide
to Biotechnology”). Transient gene therapy has been tested for the treatment of
various cancers, autoimmune diseases, chronic heart failure, nervous system
disorders, and AIDS. Id. One study found that gene therapy restored the vision of
dogs afflicted by Leber congenital amaurosis, a previously-untreatable condition
that causes almost complete blindness. Subsequent phase I trials in humans
showed a statistically significant increase in visual sensitivity in three human
subjects 30 days after treatment. Cideciyan et al., Human Gene Therapy for
RPE65 Isomerase Deficiency Activates the Retinoid Cycle of Vision But With Slow
Rod Kinetics, 105 Proc. Nat’l Acad. Sci. 15112, 15113-15114 (2008).
Vaccination. By using DNA that encodes only certain proteins from the
surface of a virus or bacteria, biotechnology innovators have been able to
manufacture vaccines carrying a lower risk of infection. Vaccines that use small
pieces of DNA to trigger antibody production also have the potential to provide
immunization against microbes for which no vaccine is currently available. Guide
to Biotechnology 34.

Genetic Testing. As with screening for HCV, patents on isolated DNA
molecules help attract investment that allows researchers to develop genetic tests to
identify hereditary diseases, test a patient’s genetic predisposition to a particular
disease, or screen for pathogens. This testing promises to usher in an era of
“personalized medicine”—also known as targeted therapy—in which knowledge
about an individual patient’s genome can help identify optimal treatments and
dosages. Between 1993 and 2009, the number of diseases for which genetic testing
is available increased from just over 100 to more than 1,800. See GeneTests,
Growth of Laboratory Directory (2000), http://www.ncbi.nlm.nih.gov/projects/
GeneTests/static/whatsnew/labdirgrowth.shtml. The current Director of the
National Institutes of Health has observed that “personalized medicine remains one
of the most compelling opportunities we have to improve the odds of staying
healthy.” Collins, Personalized Medicine, Boston Globe, July 17, 2005, at E12.
Agriculture. Researchers continue to work on ways to feed more people at
lower cost and with less environmental impact by identifying and using genetic
markers associated with natural resistance to insects and diseases, resistance to
environmental stresses such as drought and temperature fluctuations, and improved
characteristics such as lower nutrient use and higher yield. Substantial investment
is still required to unlock the full potential of DNA-based agriculture. Important
genomes, such as the cow and chicken genomes, were not sequenced until 2004.
Guide to Biotechnology 49. The corn genome, only the third of any major crop to
be sequenced, was not completed until 2008. Id. at 14. Private investment will
play a critical role in encouraging further research and translating it into important
new products that will change the way food is grown around the world.
Food Safety. The importance of DNA-based inventions to the food supply
does not end on the farm. DNA probes can detect harmful or lethal
microorganisms in the food supply. When a problem is detected, DNA
fingerprinting can be used to trace products back to their source and enable
appropriate remedial steps.

Industrial and Environmental Biotechnology. Patents on isolated DNA
molecules are also important for industrial, energy, and environmental
applications. DNA-encoded biocatalysts, such as enzymes, can decrease energy
use, replace harsh chemicals in industrial processing, and produce biofuels and
green plastics without the use of petroleum, helping to reduce dependence on
“dirty” energy sources and mitigate global climate change.

Unforeseeable Discoveries. Just as important as DNA-based research
already in progress are the unforeseen discoveries that the right incentives will
enable. As of 2008, less than one percent of the world’s microorganisms had been
cultured and characterized. Guide to Biotechnology 64. A stable patent system
that rewards the discovery, characterization, and isolation of useful DNA
molecules is critical to encouraging the private investment that will help bring
future discoveries to fruition.

B. A Decision That Isolated DNA Molecules Are Not Patent-Eligible
Would Have Far-Reaching Negative Consequences
Unless reversed, the decision below promises to cause serious harm to U.S.
biotechnological innovation. The biotechnology industry depends heavily on
patent protection to encourage the investment of time and capital necessary to
develop inventions—including those discovered industrially or in-licensed from
world-class universities in support of further academic research—into real-life
products. Biotechnological investment is substantial: 2008 saw more than $30
billion in biotechnology-related research and development investment in the
United States alone. Ernst & Young, Beyond Borders: Global Biotechnology
Report 34 (2009). The average cost of bringing a single biotechnology-related
therapeutic to market, including basic research, clinical trials, and post-approval
testing, exceeds $1.2 billion. Grabowski, Follow-On Biologics, 7 Nature Reviews
Drug Discovery 479, 482 (2008). For every successful product, many more are
abandoned, often only after large investments have been made. E.g., id. at 481
(only 30% of biological therapeutics that make it as far as human trials succeed).
In light of the high risk and difficulty involved, patents are critical to
reassuring investors that they will earn a reasonable financial return on products
that actually make it to market. This is particularly true for biotechnology
companies, most of which are emerging firms with 50 or fewer employees working
on products that can take 15 years or more to produce. Guide to Biotechnology 2,
77. Because such entities cannot fund their work on revenue from product sales,
they rely on investor capital for survival. Id. at 2.
The stage in the corporate lifecycle after the point of basic discovery but
before proof of concept has been described as the “valley of death”—a time when
companies struggle to raise the hundreds of millions of dollars needed to take their
inventions to the next stage of development. Patents—including those on isolated
DNA molecules—play a critical role in sustaining innovative companies during
this period and beyond. Patents “are typically the only assets those firms possess
that are sufficiently stable and valuable to attract the large amounts of capital they
need to exploit promising research toward new drugs and diagnostics.” Barfield &
Calfee, Biotechnology and the Patent System 27 (2007); see also Grabowski et al.,
The Market for Follow-On Biologics, 25 Health Affairs 1291, 1299 (2006)
(“Intellectual property has been an important factor for biotech start-ups in
securing venture funding and partnerships with larger firms.”). Such intellectual
property is often in-licensed from universities, which recognize that the costs and
risks of product development cannot be borne by public or non-profit entities.
E.g., AUTM, University Technology Transfer, http://www.autm.net/AM/
Template.cfm?Section=White_Papers&Template=/CM/ContentDisplay.cfm&Cont
entID=1895 (describing development of human insulin).
A ruling that isolated DNA molecules are categorically ineligible for patent
protection would shake investor confidence and interfere with the ability of
biotechnology companies, particularly small companies, to attract the capital
needed to fund further research and development. A limited preview of what
might happen came in March 2000 when investors mistakenly interpreted a
statement by President Clinton and British Prime Minister Blair as announcing an
intent to narrow patent protection for gene-based innovations. Even though the
statement was quickly clarified, leading American biotechnology companies lost
$50 billion in aggregate shareholder value over the following two weeks. Davies,
Cracking the Genome 205-207 (2001).

The decision below has even greater potential to disrupt the willingness of
investors to fund research and development. Although the district court purported
to limit its decision to isolated DNA molecules (A216 n.51), its distinction
between nucleic acids and other compositions of matter is questionable for the
reasons discussed in Part I. The decision therefore potentially casts doubt on
patent protection for a wide variety of natural substances that have been isolated
and purified (see supra §I.B), to the detriment of the biotechnology industry and
the public.

III. CLAIMS TO ISOLATED DNAMOLECULES DO NOT HARM PATIENTS OR
IMPEDE THE PROGRESS OF SCIENCE
Plaintiffs have claimed that patents on isolated DNA molecules harm
patients and stifle research. Such contentions do not withstand scrutiny. As a
Nature editorial recently summarized, opponents of DNA patenting initially
worried that patents would make it harder to develop new genetic diagnostic
tests; that corporate monopolies would hamper patients’ access to the tests;
and that thickets of interlinked intellectual property rights would scare off
those interested in researching and improving the tests.… But for all the
fuss, few, if any, of the initial concerns have been borne out.
Property Rights: The Granting of Patents on Human Genes Has So Far Not Been
the Disaster It Was Predicted To Be, 458 Nature 386 (2009). Summarizing
empirical research, the Federal Trade Commission likewise noted that “concern
previously centered on the belief that biotechnology patent protection was too
strong” and “would actually obstruct commercialization of new products, thereby
hindering follow-on innovation. This problem has yet to materialize.” FTC,
Emerging Health Care Issues 32 (2009) (footnote omitted).

A. Patents On Isolated DNA Molecules Benefit Rather Than Harm
The Public
The stories of the individual Plaintiffs in this case help explain why BIO
members have pushed so hard to encourage insurance companies with restrictive
reimbursement policies to pay for important therapeutics and diagnostics and to
establish company-sponsored plans that provide products and services to patients
who cannot afford them. A106-107, A149-150 (discussing patients whose
insurance companies would not pay for genetic testing). Plaintiffs’ effort to
abolish patents on isolated DNA molecules, however, is misdirected and shortsighted.
It mistakes problems in the insurance system for problems in the patent
system and will harm rather than help patients in the long run.
It is easy to argue after an invention has already been discovered and
disclosed that the public would be better off if it were not patented. It is just as
easy to single out a particular invention and argue with the benefit of hindsight that
patent protection was not necessary for its discovery and development. Such facile
arguments ignore the long-term benefits that the public derives from providing
patent protection in exchange for the disclosure of new and useful discoveries.
See, e.g., Eli Lilly & Co. v. Premo Pharm. Labs., Inc., 630 F.2d 120, 138 (3d Cir.
1980) (“Congress has determined that it is better for the nation in the long-run to
afford the inventors of novel, useful, and nonobvious products short-term
monopolies on such products[.]”).

The advances made by the U.S. biotechnology industry under current law
were not inevitable, and the industry’s future success depends on the ability to
continue attracting private investors willing to shoulder the substantial risk of
financing research and development. In the life sciences, early-stage companies
hold roughly two-thirds of the future clinical pipeline. Boston Consulting Group,
Rising to the Productivity Challenge 6 & Ex. 4 (2004). Without patent protection
for isolated DNA molecules, many companies would be unable to see those
projects through to completion. The list of potentially life-enhancing therapeutics
and diagnostics that die in the pipeline as a result might never be known. But their
absence would be acutely felt by patients.

B. Patents On Isolated DNA Molecules Do Not Impede The Progress
Of Science
Plaintiffs and their amici argued below that patents on “upstream”
inventions, such as isolated DNA molecules, stifle basic research. But this often30
repeated claim is largely based on speculation and a few high-profile anecdotes
rather than solid evidence. See Caulfield et al., Evidence and Anecdotes: An
Analysis of Human Gene Patenting Controversies, 24 Nature Biotech. 1091
(2006). “[E]mpirical research suggests that the fears of widespread anticommons
effects that block the use of upstream discoveries have largely not materialized.”
Id. at 1093; see also Adelman & DeAngelis, Patent Metrics, 85 Tex. L. Rev. 1677,
1681 (2007) (“The existing empirical studies find few clear signs that the patenting
of biotechnology inventions is adversely affecting biomedical innovation.”).
For example, a 2006 report by the National Research Council of the National
Academies found that the number of projects abandoned or delayed as a result of technology
access difficulties is reported to be small, as is the number of occasions in
which investigators revise their protocols to avoid intellectual property
complications or pay high costs to obtain access to intellectual property.
Thus, for the time being, it appears that access to patents or information
inputs into biomedical research rarely imposes a significant burden for
academic biomedical researchers.

National Research Council, Reaping the Benefits of Genomic and Proteomic
Research 134 (2006).
A 2005 survey of scientists involved in biomedical research found that
“patenting does not seem to limit research activity significantly, particularly among
those doing basic research.” Walsh et al., Patents, Material Transfers and Access
to Research Inputs in Biomedical Research 3 (Sept. 20, 2005), available at
31
http://www2.druid.dk/conferences/viewpaper.php?id=776&cf=8 (“Walsh, Patents
& Access”). Only one percent of a random sample of 381 academic scientists
reported a project delay of more than a month due to patents on materials
necessary for their research, and none reported abandoning a research project due
to the existence of patents. Id. at 17; see also Walsh et al., View from the Bench,
309 Science 2002 (2005).

An earlier study found that patents “rarely precluded the pursuit of
worthwhile projects.” Walsh et al., Working Through the Patent Problem, 299
Science 1021, 1021 (2003). It noted that “for a given project, usually fewer than a
dozen outside patents require serious consideration, and the number of licenses
required is much fewer, often none.” Id. When requested, licenses were often
available at minimal or no cost. Walsh, Patents & Access, at 17. “Thus, not only
are barriers or delays rare, but costs of access for research purposes are negligible.”
Id.

Anecdotes regarding specific instances of patent enforcement, such as those
involving Myriad (e.g., A152-155), fall far short of demonstrating that patents on
isolated DNA impede research. As an initial matter, it is important not to confuse
the ordinary assertion of patent rights against commercial competitors with limits
on basic research. “Myriad appears to have never asserted its patents based on
genetic testing research, but only against substantial direct commercial competitors.” Holman, The Impact of Human Gene Patents on Innovation and
Access, 76 UMKC L. Rev. 295, 347 (2007). Indeed, a vast amount of BRCArelated
clinical and experimental research has been conducted since Myriad’s
patents issued. See A5570-5575; see also Huys et al., Legal Uncertainty in the
Area of Genetic Diagnostic Testing, 27 Nature Biotech. 903, 909 (2009) (“[T]he
present analysis and accompanying observations do not point to the existence of a
wide patent thicket in genetic diagnostic testing.”). Arguments about stifling
research also ignore the protection provided to researchers under 35 U.S.C.
§271(e)(1), see Merck KGaA v. Integra Lifesciences I, Ltd., 545 U.S. 193 (2005),
and the common law research exception, see Whittemore v. Cutter, 29 F. Cas.
1120, 1121 (C.C.D. Mass. 1813) (Story, J.).

More fundamentally, anecdotes about a single company or single field of use
hardly provide a sound basis for eliminating all patents on isolated DNA
molecules. The public has been well served by the USPTO’s position that isolated
DNA molecules are patent-eligible subject matter and its reliance on other, more
carefully tailored doctrines to block patents that should not issue. See supra p. 10.
If a different balance is to be struck, it should be struck by Congress based on
sound evidence and with due regard to the reliance interest of existing patentholders,
rather than by the courts based an anecdotal evidence about one particular
patent-holder.