No. 08-964 
In The 
Supreme Court of the United States 
----------------- ♦ ----------------- 
----------------- ♦ ----------------- 
On Writ Of Certiorari To The 
United States Court Of Appeals 
For The Federal Circuit 
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----------------- ♦ ----------------- 
  Counsel of Record 
1301 Avenue of the Americas, 
New York, NY 10019 
(212) 999-5800 
Attorneys for Amicus Curiae 
  Caris Diagnostics, Inc. 
OR CALL COLLECT (402) 342-2831 

INTEREST OF AMICUS CURIAE ........................   

SUMMARY OF ARGUMENT ................................  

ARGUMENT ...........................................................  

ESSES ..........................................................  

CONCLUSION .......................................................   32 

Classen Immunotherapies, Inc. v. Biogen IDEC
No. 2006-1634, 2008 WL 5273107 (Fed. Cir. 
Dec. 19, 2008) .......................................................... 21 
Diamond v. Chakrabarty, 447 U.S. 303 
(1980) ................................................... 8,  9, 10, 12, 31 
Diamond v. Diehr, 450 U.S. 175 (1981) ............. passim 
Festo v. Shoketsu Kinzoku Kogyo Kabushiki 
Co., 535 U.S. 722 (2002) .......................................... 24 
Funk Bros. Seed Co. v. Kalo Inoculant Co., 333 
U.S. 127 (1948) .................................................. 10,  11 
Gottschalk v. Benson, 409 U.S. 63 (1972) .......... passim 
In re Bilski, 545 F.3d 943 (Fed. Cir. 2008) ......... passim 
J.E.M. Ag Supply, Inc. v. Pioneer Hi-Bred Int’l, 
Inc., 534 U.S. 124 (2001) ........................................... 9 
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398 
(2007) ....................................................................... 12 
King Pharms., Inc. v. Eon Labs, Inc., 593 
F. Supp. 2d 501 (E.D.N.Y. 2009) ............................. 21 
Lab. Corp. of Am. v. Metabolite Labs., Inc., 548 
U.S. 124 (2006) .................................................. 18, 19 
Mackay Radio & Telegraph Co. v. Radio of Am.
306 U.S. 86 (1939) ................................................... 11 
Parker v. Flook, 437 U.S. 584 (1978) ................. passim 

Payne v. Tennessee, 501 U.S. 808 (1991) .................... 24 
Warner-Jenkinson Co. v. Hilton Davis Chemical 
Co., 520 U.S. 17 (1997)............................................ 24 
35 U.S.C. § 100(b) ......................................................... 9 
35 U.S.C. § 101 ................................................... passim 
35 U.S.C. § 102 ............................................................. 9 
35 U.S.C. § 103 ....................................................... 9, 12 
35 U.S.C. § 112 .............................................................. 9 
35 U.S.C. § 287(c) ....................................................... 31 
5 Writings of Thomas Jefferson (Washington 
ed. 1871) .................................................................. 12 
Astrid Lievre et al., KRAS Mutations As an 
Independent Prognostic Factor in Patients 
With Advanced Colorectal Cancer Treated 
With Cetuximab, 26 J. Clinical Oncology 374 
(Jan. 20, 2008) ........................................................... 2 
Christos S. Karapetis, M.D., et al.,  K-ras 
Mutations and Benefit from Cetuximab in 
Advanced Colorectal Cancer, 359 New Eng. J. 
Med. 1757 (Oct. 23, 2008) ......................................... 2 
Gina-Louise Monari, Pressure rises in cardio, 
MedAd News, Feb. 2009 ......................................... 30 

Glen T. Giovannetti & G. Jaggi, Ernst & Young, 
Beyond Borders – Global Biotechnology 
Report 2009 (2009) .................................................. 30 
John J. Love, Deputy Commissioner for Patent 
Examination Policy to the Technology Center 
Directors and Patent Examining Corps, 
Memorandum dated January 7, 2009 .............. 21, 22 
Kathleen Bragdon, Quality Assurance 
Specialist, Technology Center 1600, USPTO, 
A Look at Personalized Medicine ............................ 21 
Lifetime Probability of Developing or Dying 
from Cancer, American Cancer Society, July 
13, 2009 ..................................................................... 4 
Merck Plans More Cost-Cutting, N.Y. TIMES, 
Dec. 16, 2005 ........................................................... 30 
Paul H. Keckley, PhD et al., Deloitte Center for 
Health Solutions, The ROI for Targeted 
Therapies:  A Strategic Perspective Assessing 
the Barriers and Incentives for Adopting 
Personalized Medicine (2009) ................................... 3 
Roxanne Nelson, GICS 2009: Huge Cost 
Savings From KRAS Testing in Metastatic 
Colorectal Cancer, Medscape Medical News, 
Jan. 16, 2009 ............................................................. 3 

Amicus curiae Caris Diagnostics, Inc. (“Caris”) is 
a leader in personalized medicine, which is the 
relatively new science of tailoring therapeutics for 
individual patients through diagnostic tests for 
genetic mutations known as biomarkers. By using 
such molecular profiling techniques, Caris enables 
patients to receive safe and effective drug therapies 
for cancer and other serious illnesses.  
  For example, Caris’s laboratories examine 
tumors to discover biomarkers that are associated 
with drug resistance or toxicity. A recent study 
showed that cetuximab (or Erbitux®), a standard 
treatment for colorectal cancer, shrinks tumors in 
40% of patients lacking a particular genetic mutation 
1 Counsel  for  amicus appear in this matter in their 
individual capacities and not on behalf of the law firm with 
which they are affiliated. Counsels’ law firm represents many 
technology companies operating in diverse business sectors, 
including biotechnology, electronics, software, and internet 
companies, and such companies may have different opinions on 
the issues presented by the Federal Circuit’s decision below. 
Nothing in this brief should be attributed or imputed to 
counsels’ law firm or its clients, other than those specific ones on 
whose behalf this brief is filed.  
Counsel for all parties have consented to the filing of this 
brief, and their consents have been lodged with the Clerk of this 
Court. No counsel for any party had any role in authoring this 
brief, and no person other than the named amicus and its 
counsel has made any monetary contribution to the preparation 
and submission of this brief.  See Rule 37. 

but is ineffective in patients possessing the mutation.2 
Before the sequencing of the human genome and the 
possibility of fast, affordable, and accurate tests for 
individualized genetic profiles, the treatment would 
be prescribed generally to colorectal cancer patients, 
and only time would tell which subpopulation of 
patients would have treatment-resistant tumors.  
Now that biomarkers for resistance to the drug 
have been discovered, and Caris has developed tests 
for those biomarkers, an oncologist need not waste 
valuable time with hit-and-miss treatment. Instead, 
to obtain early validation of drug choices, the 
oncologist sends a biopsy to Caris – one of thousands 
of biopsies that Caris examines daily – which then 
determines whether the particular patient’s tumor 
has the biomarker associated with drug resistance. 
Caris’s development and provision of such biomarker 
tests3 thus enable doctors to devote critical months to 
effective treatments. Caris’s work thereby saves lives 
2 See Astrid Lievre et al., KRAS Mutations As an Inde-
pendent Prognostic Factor in Patients With Advanced Colorectal 
Cancer Treated With Cetuximab, 26 J. Clinical Oncology 374, 375 
(Jan. 20, 2008), available at 
full/26/3/374;  see also Christos S. Karapetis, M.D., et al.,  K-ras 
Mutations and Benefit from Cetuximab in Advanced Colorectal 
Cancer, 359 New Eng. J. Med. 1757, 1757-65 (Oct. 23, 2008), 
available at 
3 Such biomarker tests when used to diagnose a patient’s 
illness or medical condition are known as diagnostics, and when 
used to diagnose a patient’s resistance to a particular drug are 
known as theragnostics. For simplicity, the term “diagnostics” as 
used herein refers to both diagnostics and theragnostics.  

– as well as the several hundred million dollars that 
would otherwise be spent on useless, expensive 
In patent terms, each biomarker test is a method 
for determining the presence of the biomarker in a 
given patient. A process patent provides the soundest 
legal protection for the intellectual property under-
lying each such method, and thus provides the 
strongest incentive for venture capitalists and large, 
established companies to invest – and hence fund 
research, development, regulatory approval, and 
commercialization – in hopes of obtaining a return in 
the marketplace. Since roughly half of Americans will 
get cancer before dying, and about half of these will 
4 Roxanne Nelson, GICS 2009: Huge Cost Savings From 
KRAS Testing in Metastatic Colorectal Cancer, Medscape 
Medical News, Jan. 16, 2009, available at http://www.medscape. 
com/viewarticle/586946 (screening for KRAS mutations before 
initiating treatment with cetuximab or related drugs could 
result in drug cost savings of $604 million if annual American 
population with metastatic colorectal cancer undergoes first-line 
therapy with cetuximab-containing regimen). The savings to the 
U.S.  health  care  system  from  genetic profiling to optimize 
treatment with a single drug are estimated to be more than $1 
billion.  See  Paul  H.  Keckley,  PhD  et  al.,  Deloitte  Center  for 
Health Solutions, The ROI for Targeted Therapies: A Strategic 
Perspective Assessing the Barriers and Incentives for Adopting 
Personalized Medicine, at 5 (2009) (fig. 2), available at http:// 
ROIforTargeted%20Therapies_DCHSstudy_FINAL.pdf (estimated 
potential annual health care cost savings from individual dosing 
of Warfarin based on genetic testing are $1.1 billion with a range 
of $100 million to $2 billion for U.S. health care system). 

die of their cancer,5 continued financing is important 
not only to Caris and other diagnostics companies but 
also to public health.  
In re Bilski, 545 F.3d 943 (Fed. Cir. 2008), 
which involved a claim for a business method, the 
United States Court of Appeals for the Federal 
Circuit held that the exclusive test for determining 
whether a process claim recites patentable subject 
matter under 35 U.S.C. § 101 is whether the claim is 
(a) tied to a machine or (b) transforms an article into 
a different state or thing. Only by misapplying this 
Court’s precedents did the Federal Circuit reach its 
holding. Further, by mandating the machine-or-
transformation test for all  process claims (not just 
business method claims), the Federal Circuit 
drastically narrowed the scope of patentable subject 
matter, undermined the settled expectations of 
owners of process patents, raised doubt as to the legal 
protection of new diagnostic and treatment methods, 
and diminished the ability of biotechnology com-
panies to attract investment capital. Particularly in 
an economy increasingly based on information and 
biotechnology, the outmoded “machine tie” and 
“transformation” analyses are too uncertain of 
5 See  Lifetime Probability of Developing or Dying from 
Cancer, American Cancer Society, July 13, 2009, available at http:// 
of_developing_or_dying_from_cancer.asp (indicating about 1 in 2 
males and 1 in 3 females will develop cancer in their lifetime, 
and 1 in 4 and 1 in 5, respectively, will die from cancer). 

application to provide such companies with genuine 
legal protection. Moreover, the U.S. Patent and 
Trademark Office (“USPTO”) has now adopted new 
guidelines for review of life sciences patents and is 
routinely rejecting patents based on the decision 
below. Without such patent protection, Caris and 
other biotechnology companies will face a shortage of 
funding and hence will be unable to make critical 
discoveries and to translate them into improved 
patient care. It is not an overstatement to say that 
biotechnology companies depend for their survival on 
strong patent protection, as only the limited 
exclusivity of patents will genuinely compensate such 
companies and their investors for their significant 
research and regulatory costs, and for assuming the 
risk of biological obstacles and fierce marketplace 
Accordingly, Caris has a strong interest in 
ensuring that the decision below is reversed insofar 
as it held the machine-or-transformation test to be 
the exclusive test for patentable subject matter in 
process claims. 
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The judgment of the Federal Circuit should be 
reversed insofar as it held the machine-or-
transformation test to be the exclusive test for the 
patentability of claimed processes under 35 U.S.C. 
§ 101. Subject matter is patentable if it fits into one of 

the four statutory categories – process, machine, 
manufacture, composition of matter – and is useful 
and man-made. Nothing in the statute or this Court’s 
precedents requires that, to be patentable, a process 
must either be tied to a machine or transform an 
article into a different state or thing. Only 
fundamental principles – laws of nature, natural 
phenomena, and abstract ideas – are unpatentable 
subject matter, though an application of a funda-
mental principle is patentable if useful and inventive. 
These flexible standards governing patentability 
should not be replaced with a rigid, Industrial-Age 
rule requiring the presence of machinery or physical 
transformation. Such a rule would bar vast areas of 
innovation from patent protection and would 
therefore be contrary to Congress’s intent that 
patentable subject matter be broad in scope. 
Twice, this Court has ruled expressly that the 
machine-or-transformation test is not the exclusive 
test for the patentability of a process under § 101. 
The Federal Circuit misinterpreted both decisions by 
baselessly reading into them a directive of exclusivity 
and by wholly ignoring the decisions’ express 
rejection of exclusivity. The essential holding of the 
decisions is that a process claim may not preempt a 
fundamental principle, and not that machine imple-
mentation and transformation are the exclusive 
means by which a process claim can avoid such 

The decision below dramatically weakens patent 
protection for diagnostics and thus will chill invest-
ment and innovation. Although certain steps of some 
diagnostic methods involve machines or trans-
formations, the focus of diagnostic methods is the 
generation of information. Thus, it is unclear if 
machine implementation and transformation are 
sufficiently central to each method to satisfy the 
machine-or-transformation test. Such doubt will 
discourage investment by venture capitalists and 
larger, mature companies, because of resulting 
uncertainty as to whether future diagnostic 
innovations will receive patent protection. Moreover, 
the decision below applies the machine-or-
transformation test to all claimed processes – 
including diagnostic methods – and not just business 
methods. Consequently, diagnostic method claims are 
already being rejected under Bilski, and many 
already-issued patents are now subject to invalidity 
defenses in infringement litigation. 
  Without the limited exclusivity of patent 
protection, health care companies and their investors 
will lose incentive to research, develop, and com-
mercialize new diagnostics. The decision below 
constitutes the sort of fundamental change in settled 
patent law that only Congress is equipped to make. 
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Under this Court’s precedents, patentable subject 
matter under 35 U.S.C. § 101 consists of any man-
made and useful process, machine, manufacture, or 
composition of matter, but must not be laws of 
nature, natural phenomena, or abstract ideas. Lest 
lower courts usurp Congress’s function, this Court 
has warned that “courts should not read into the 
patent laws limitations and conditions which the 
legislature has not expressed.” Diamond v. 
Chakrabarty,  447 U.S. 303, 308 (1980) (citation and 
internal quotation marks omitted). Moreover, this 
Court has twice held that subject matter may be 
patentable even if it does not satisfy the machine-or-
transformation test. See Gottschalk v. Benson, 409 
U.S. 63, 71 (1972); Parker v. Flook, 437 U.S. 584, 588 
n.9 (1978). Contrary to the statute and these clear 
holdings, however, the court below held that a process 
claim cannot recite patentable subject matter under 
35 U.S.C. § 101 unless it also satisfies the machine-
or-transformation test. That holding is erroneous and 
should be reversed. 

Section 101 is broadly worded: 
Whoever invents or discovers any  new and 
useful process, machine, manufacture, or 
composition of matter, or any new and useful 
improvement thereof, may obtain a patent 
therefor, subject to the conditions and 
requirements of this title. 
35 U.S.C. § 101 (emphasis added).6 According to the 
plain statutory language, subject matter is patentable 
as long as it fits into one of the four categories – 
process, machine, manufacture, composition of matter 
– and is useful and man-made.7 As the repeated use 
of the term “any” indicates, “Congress plainly con-
templated that the patent laws would be given wide 
scope.”  Chakrabarty,  447 U.S. at 308. In J.E.M. Ag 
Supply, Inc. v. Pioneer Hi-Bred Int’l, Inc., 534 U.S. 
124 (2001), this Court stated that § 101 is “extremely 
broad,”  id.  at 130, and is a “dynamic provision 
designed to encompass new and unforeseen inven-
tions,”  id.  at 135. Nothing on the face of the statute 
6 According to the statutory definitional provision, “[t]he 
term ‘process’ means process, art or method, and includes a new 
use of a known process, machine, manufacture, composition of 
matter, or material.” 35 U.S.C. § 100(b). 
7 Although § 101, which addresses patent eligibility of 
subject matter, also uses the term “new,” it has long been held 
that novelty and non-obviousness should be addressed under 
§§ 102 and 103. 35 U.S.C. §§ 102, 103. 35 U.S.C. §§ 102, 103. 
See, e.g.,  Diamond v. Diehr, 450 U.S. 175, 189-91 (1981). Addi-
tional safeguards against undeserved grants of patent protection 
appear in § 112, which imposes the requirements of enablement, 
written description, and definiteness.  35 U.S.C. § 112. 

requires that, to be patentable, a process (i) be tied to 
a machine (or, for that matter, to a manufacture or 
composition of matter) or (ii) transform an article into 
a different state or thing.8  
This Court’s only limiting gloss on § 101 is that 
fundamental principles – “laws of nature, natural 
phenomena, and abstract ideas” – are not patentable 
subject matter. Chakrabarty,  447 U.S.  at 309. The 
reason is that such principles, like mental processes, 
“are the basic tools of scientific and technological 
work.” Benson, 409 U.S. at 67; Flook, 437 U.S. at 589, 
593 n.15; Funk Bros. Seed Co. v. Kalo Inoculant Co., 
333 U.S. 127, 130 (1948) (“[Fundamental principles] 
are part of the storehouse of knowledge of all men. 
They are . . . free to all men and reserved exclusively 
to none.”). However, an application  of a fundamental 
principle can be patentable under § 101, provided the 
application is useful and inventive. See Flook, 437 
U.S. at 594 (“[E]ven though a phenomenon of nature 
or mathematical formula may be well known, an 
inventive application of the principle may be 
8  The Federal Circuit itself acknowledged that the machine-
or-transformation test does not appear on the face of the statute. 
Bilski, 545 F.3d at 956 n.11 (“the statute itself does not explicitly 
mention machine implementation or transformation”). As one of 
the dissents below stated, “The United States Supreme Court 
has never held that ‘process’ inventions suffered a second-class 
status under our statutes, achieving patent eligibility only 
derivatively through an explicit ‘tie’ to another statutory 

. Yet second-class status is today engrafted on 
‘process’ inventions.” Id. at 990 (Newman, J., dissenting).  

patented.”);  Funk Bros., 333 U.S. at 1309 (“He who 
discovers a hitherto unknown phenomenon of nature 
has no claim to a monopoly of it which the law 
recognizes. If there is to be invention from such 
discovery, it must come from the application of the 
law of nature to a new and useful end.”).10 If the 
fundamental principle cannot be applied except in a 
single, limited fashion, then no patent may be 
granted on the application; if granted, such a patent 
would preempt the fundamental principle and hence, 
in effect, be a patent on the principle itself. Benson, 
409 U.S. at 71-72. If the claim is drawn so broadly, or 
is so unrelated to any particular use of a fundamental 
principle, that it preempts substantially all uses of 
that principle, it is similarly unpatentable. Id. at 68-
The question here is whether, in the case of a 
process claim, the foregoing standards need to be 
supplemented, or even supplanted, by an exclusive 
and rigid rule for distinguishing between a 
9 Although  Funk Bros. concerned a product claim, its 
holding applies to a process claim. Diehr, 450 U.S. at 188 n.11 
(citing Benson, 409 U.S. at 68). 
10 See also  Diehr, 450 U.S. at 187 (“It is now commonplace 
that an application of a law of nature or mathematical formula 
to a known structure or process may well be deserving of patent 
protection.”);  Mackay Radio & Telegraph Co. v. Radio of Am.
306 U.S. 86, 94 (1939) (“While a scientific truth, or the 
mathematical expression of it, is not a patentable invention, a 
novel and useful structure created with the aid of knowledge of 
scientific truth may be.”). 

fundamental principle and a patentable application 
thereof. In Caris’s view, no such supplementation is 
needed: The rule in question, the machine-or-
transformation test, would replace flexible standards 
– whose merit lies in their ability to accommodate 
new and unforeseen technologies – with an unduly 
limited choice, conditioning patentability on the 
presence of either machinery or physical transforma-
tion.11 The language of the test impermissibly looks 
backward to the brute physicality of the Industrial 
Age rather than forward to the subtle realities of the 
Information Age. As articulated by Thomas Jefferson, 
author of the nation’s first patent legislation, the goal 
of the Patent Act is that “ ‘ingenuity should receive a 
liberal encouragement.’ ” Chakrabarty,  447 U.S. at 
308 (quoting 5 Writings of Thomas Jefferson 75-76 
(Washington ed. 1871)). Mandating the machine-or-
transformation test would bar vast areas of 
innovation from such encouragement and thus would 
be contrary to congressional intent. 
In assessing the patentability of process claims, 
this Court has never required the machine-or-
transformation test and has twice ruled that it is not 
the exclusive patentability test for such claims. In 
Benson,  the Court, after reviewing its decisions 
11 This Court has recognized that rigid tests are often 
inadequate for addressing patentability. See KSR Int’l Co. v. 
Teleflex Inc., 550 U.S. 398, 415 (2007) (“We begin by rejecting the 
rigid approach” used by lower court for determining pat-
entability under 35 U.S.C. § 103). 

sustaining patents on the basis of a transformation 
involving no machine, held: 
It is argued that a process patent must either 
be tied to a particular machine or apparatus 
or  must  operate to change articles or 
materials to a ‘different state or thing.’ We do 
not hold that no process patent could ever 
qualify if it did not meet the requirements of 
our prior precedents. 
409 U.S. at 71 (emphasis added).12 This express 
holding that the machine-or-transformation test is 
not the exclusive test for the patentability of claimed 
processes was reaffirmed in Flook
The statutory definition of “process” is 

. An argument can be made, 
however, that this Court has only recognized 
a process as within the statutory definition 
when it either was tied to a particular 
apparatus or operated to change materials to 
a “different state or thing.” . . . As in Benson, 
we assume that a valid process patent may 
issue even if it does not meet one of these 
qualifications of our earlier precedents
12  Inexplicably, the majority below called these statements 
“equivocal.” 545 F.3d at 956. As Judge Newman’s dissent 
observed, there is nothing equivocal about the phrase “We do not 
hold . . . .” See id. at 979 (Newman, J., dissenting).  

437 U.S. at 588 n.9 (emphasis added) (citations 
omitted).13 Thus, the Court concluded that while 
claims to processes have been upheld when the 
process at issue was in fact tied to a machine or 
transformed an article into a different state or thing, 
nothing in the Court’s holdings has elevated either a 
machine tie or a transformation into the sine qua non 
of patentability or has turned such facts into legal 
In view of Flook  and  Benson, the principal basis 
for the Federal Circuit’s holding may be quickly 
rejected. The holding was based on the following 
sentence from Benson,  which the majority below 
quoted three times: “Transformation and reduction of 
an article ‘to a different state or thing’ is the clue to 
the patentability of a process claim that does not 
include particular machines.” Benson, 409 U.S. at 70; 
see Bilski, 545 F.3d at 954, 955-56, 956. According to 
the Federal Circuit, the Benson  Court’s use of the 
definite article “the” – instead of the indefinite article 
“a” – before the word “clue” proved that the Court 
meant the machine-or-transformation test to be the 
exclusive test for the patentability of a process. See 
Bilski,  545 F.3d at 955-56 & n.11. Moreover, the 
Federal Circuit, noting that Diehr  repeated  Benson’s 
“clue” sentence without repeating Benson’s  and 
Flook’s holding of non-exclusivity, essentially held 
13  The majority below tendentiously omitted the phrase “An 
argument can be made” from its quotation of this portion of 
Flook.  See 545 F.3d at 956. 

that  Diehr  overruled these non-exclusivity holdings 
sub silentio. For several reasons, the Federal Circuit’s 
conclusions are fatally flawed.  
First, if the Benson  Court had wanted to make 
transformation the exclusive legal test of patent-
ability for a process untied to a machine, it would 
have used language far more definite than the 
hesitant and unemphasized phrase “the clue.”  
Second, the quite debatable sentence on which 
the Federal Circuit relied appears in the same 
Benson  opinion as the explicit holding that a process 
may be patentable even if it involves no machine 
implementation or transformation. Because the Court 
that authored the proposition relied on by the Federal 
Circuit also held the proposition non-exclusive, any 
argument for exclusivity is foreclosed.  
Third, the Federal Circuit’s argument that Diehr 
relied on Benson’s “clue” sentence but did not repeat 
Benson’s holding of non-exclusivity, see Bilski, 545 
F.3d at 956, proves nothing. The process at issue in 
Diehr involved a machine – a rubber molding press – 
and transformed raw rubber into cured rubber. 450 
U.S. at 180, 184. The Court held the process 
patentable.  Id.  But nothing in the holding remotely 
stated that a process that involves neither a machine 
nor a transformation cannot be patentable.14 That 
14 An additional reason why Diehr did not hold that a 
process involving no machine or transformation is unpatentable 
under § 101 is that the process at issue there involved both a 
(Continued on following page) 

statement was so firmly rejected in Benson and Flook 
that the rejection simply did not need repeating in 
Diehr.  Had the Diehr  Court understood itself to be 
overruling the explicit non-exclusivity holdings of 
Benson  and  Flook,  the majority opinion in Diehr 
would surely have mentioned that understanding. 
That it did not do so demonstrates that the non-
exclusivity holdings of Benson and Flook remain good 
law after Diehr.  
Fourth, the Diehr Court itself described Benson 
and Flook as holding no more than that a 
fundamental principle is unpatentable. 450 U.S. at 
185. That is, the raison d’etre of a machine tie or a 
transformation was to avoid patenting a fundamental 
principle – meaning that if a process claim found 
some other way to avoid claiming a fundamental 
principle, then that claim would be patentable under 
§ 101.  See Bilski, 545 F.3d at 1013 (“The Supreme 
Court stated that all of the transformation and 
machine linkage explanations simply restated the 
abstractness rule.” (Rader, J., dissenting)). In other 
words, the Benson  Court’s holding was that the 
process claim there preempted a mathematical 
formula (and thus was not drawn to patentable 
subject matter), and not that the machine-or-
transformation test is the only means by which a 
process claim can avoid such preemption. 
machine and a transformation. See Bilski, 545 F.3d at 981 
(Newman, J., dissenting). As a result, the issue of whether a 
process involving no machine or transformation is patentable 
was not squarely presented.  

Diehr shows that the Federal Circuit, by 
focusing on machinery and transformation, confused 
instantiation of the governing standards with the 
standards themselves. Diehr held that 
when a claim containing a mathematical 
formula implements or applies that formula 
in a structure or process which, when 
considered as a whole, is performing a 
function which the patent laws were 
designed to protect (e.g., transforming or 
reducing an article to a different state or 
thing), then the claim satisfies the require-
ments of § 101. 
450 U.S. at 192 (emphasis added). If transformation 
had been a critical requirement of the Court’s 
holding, it would not have been mentioned in a 
parenthetical aside, and it would not have been 
introduced by “e.g.” Indeed, the use of “e.g.” implies, 
contrary to the exclusivity of the Federal Circuit’s 
holding, that any number of means besides trans-
formation might be employed to ensure that the claim 
is drawn to a patentable process rather than an 
unpatentable fundamental principle. 
The Federal Circuit’s decision should accordingly 
be reversed. 

Venture capital is the lifeblood of biotechnology 
companies and their life-saving discoveries. But 
venture capitalists and established companies will 
make few investments unless the discoveries receive 
strong patent protection. Any uncertainty in the 
availability of such protection will chill investment 
and hence innovation. For several reasons, the 
decision below, which is not limited to business 
methods and applies to all processes in every field of 
endeavor, will dramatically weaken patent protection 
for diagnostics, and thus will jeopardize funding for 
the entire industry.  
Patents for diagnostics often claim a two-step 
method that consists of a non-specific assay or other 
measurement, followed by a correlation between the 
assay result and a disease, medical condition, or 
resistance to a particular treatment.15 The focus of 
15 In dissent below, Judge Rader, addressing questions 
raised in the dissent from the dismissal of the writ of certiorari 
granted in Laboratory Corporation of America v. Metabolite 
Laboratories, Inc., 548 U.S. 124, 125-39 (2006), cogently 
explained why such diagnostic method claims recite patentable 
subject matter under § 101: 
That dissent is premised on a fundamental 
misapprehension of the distinction between a natural 
phenomenon and a patentable process. . . . 
(Continued on following page) 

each such method is the generation of information 
useful for diagnosis and treatment. While the first 
step in such methods is often – though not always – 
an assay that employs a machine or apparatus (such 
as a computer, thermocycler, gas chromatograph, 
gene chip, and/or mass spectrophotometer) and 
transforms components of tissue or blood samples 
into detectible chemical complexes (such as antibody-
protein or nucleic acid complexes),16 it is and will 
The fundamental error in that Lab. Corp. dissent is 
its failure to recognize the difference between a patent 
ineligible relationship – i.e., that between high homo-
cysteine levels and folate and cobalamin deficiencies – 
and a patent eligible process for applying that 
relationship to achieve a useful, tangible, and concrete 
result – i.e., diagnosis of potentially fatal conditions in 
patients. . . . Moreover, testing blood for a dangerous 
condition is not a natural phenomenon, but a human 
    The distinction is simple but critical: A patient 
may suffer from the unpatentable phenomenon of 
nature, namely high homocysteine levels and low 
folate. But the invention does not attempt to claim 
that natural phenomenon. Instead the patent claims a 
process for assaying a patient’s blood and then 
analyzing the results with a new process that detects 
the life-threatening condition. Moreover, the sick 
patient does not practice the patented invention. 
Instead the patent covers a process for testing blood 
that produces a useful, concrete, and tangible result: 
incontrovertible diagnostic evidence to save lives. 
Bilski, 545 F.3d at 1013-14 (Rader, J., dissenting). 
16  Not every diagnostic method patent involves an assay, 
however. When a diagnostic method involves no assay, it 
may be particularly vulnerable to rejection under the 
(Continued on following page) 

remain doubtful whether machine implementation 
and transformation are sufficiently central to each 
method to satisfy the machine-or-transformation test. 
See Bilski, 545 F.3d at 961-62 (“The use of a specific 
machine or transformation or an article must impose 
meaningful limits on the claim’s scope . . . . Th[e] 
transformation must be central  to the purpose of the 
claimed process.” (emphasis added)); id.  at 1015 
(Rader, J., dissenting) (“[The majority] opinion 
propagates  unanswerable  questions: What form or 
amount of transformation suffices? . . . What link to a 
machine is sufficient to invoke the ‘or machine’ 
prong?” (emphasis added)).17 Such doubt creates a 
significant disincentive for investment because of the 
consequent uncertainty as to whether future inno-
vations in molecular diagnostics will be accorded pat-
ent protection.  See Bilski, 545 F.3d at 1014 (Rader, J., 
dissenting) (“[T]his court inadvertently advises 
investors that they should divert their unprotectable 
investments away from discovery of ‘scientific 
relationships’ within the body that diagnose breast 
cancer or Lou Gehrig’s disease or Parkinson’s . . . .”). 
machine-or-transformation test, as the discussion below 
concerning the ’180 Office Action reveals. 
17  Because of the risk inherent in myopic attention to only 
one step in a process, Diehr warns that a court, in assessing the 
patentability of a claimed process, must consider the claim “as a 
whole.”  Diehr,  450 U.S. at 188. Yet the majority opinion below 
runs afoul of this admonition by requiring that, in a process 
claim, the step involving a transformation – such as might occur 
during the assay step of a two-part diagnostic method – be 
“central” to the process.  545 F.3d at 962. 

The danger to personalized medicine is clear. 
Before the year was out, the Federal Circuit had used 
the decision below to invalidate claims in a patent for 
an immunization method. See  Classen Immuno-
therapies, Inc. v. Biogen IDEC, No. 2006-1634, 2008 
WL 5273107 (Fed. Cir. Dec. 19, 2008); see also King 
Pharms., Inc. v. Eon Labs, Inc., 593 F. Supp. 2d 501, 
512-13 (E.D.N.Y. 2009) (invalidating treatment 
method claim under Bilski). On December 3, 2008, in 
a presentation concerning personalized medicine, the 
USPTO explicitly applied the holding below to a 
theragnostic method for selecting a treatment for 
breast cancer18 – belying Respondent’s assertion in its 
opposition to certiorari that this matter implicates 
only business methods and not “frontier tech-
nologies,” see Brief for the Respondent in Opposition, 
Bilski v. Doll, No. 08-964, 2009 WL 1179332, at *14 
(Sup. Ct. May 1, 2009). Early in 2009, the USPTO 
issued guidelines to patent examiners for applying 
the machine-or-transformation test to process claims 
in view of the decision below.19 The guidelines stated 
that “reciting a specific machine or a particular 
18 See  Kathleen Bragdon, Quality Assurance Specialist, 
Technology Center 1600, USPTO, A Look at Personalized 
Medicine, at slide 16, available at 
19 See Memorandum dated January 7, 2009, from John J. 
Love, Deputy Commissioner for Patent Examination Policy to 
the Technology Center Directors and Patent Examining Corps 
(“Bilski Guidance Memo”), available at 

transformation of a specific article in an insignificant 
step, such a[s] data gathering or outputting, is not 
sufficient to pass the test.” Bilski Guidance Memo at 
1. Left unclear, however, is whether an assay or other 
measurement constitutes “data gathering.” 
USPTO Examiners have begun rejecting diag-
nostic method claims under Bilski. On July 7, 2009, 
an Examiner rejected U.S. Application Serial No. 
10/888,18020 (the “ ’180 Office Action”), claim 1 of 
which was rejected under Bilski. Claim 1 described a 
method for detecting endometrial pathology by 
detecting a plurality of polypeptides in a test sample 
to obtain a test profile, comparing the test profile to a 
reference protein profile, and determining that a 
patient has an endometrial pathology where a 
difference is measured with respect to at least one 
biomarker. Acknowledging the holding below,  the 
Examiner asserted that a claimed process is pat-
entable only if it meets the machine-or-
transformation test. ’180 Office Action, p. 4 (citing 
Bilski),  available at 
portal/pair (Application No. 10/888,180; file wrapper). 
The Examiner then stated that “the claimed subject 
matter recites steps for obtaining a patient’s sample, 
detecting polypeptides in the test sample to yield a 
profile, and providing a result to a user in a user 
20  Assigned to Science & Technology Corporation (STC.UNM) 
at University of New Mexico, on reel/frame no. 021321/0457, 
recorded 7/31/2008, available at 
assignments/q?db=pat (Published Application No. 20050100967). 

readable format without requiring any specific 
machines for performing these steps.”  Id. (emphasis 
added). Finally, the Examiner stated that the 
“claimed subject matter recites steps for obtaining a 
patient sample and detecting polypeptides . . . [but 
that] . . . these limitations do not require any assays 
for performing these steps and therefore do not 
explicitly result in a transformation of an article.” Id
(emphasis added).21 Similar rejections are certain to 
It is not just pending applications that are now in 
jeopardy: Hundreds, even thousands, of already-
issued patents are now subject to invalidity defenses 
in infringement litigation. Many such patents recite 
diagnostic methods involving neither an assay (or 
other transformative measurement) nor machine 
implementation. Many others involve an assay in 
which the transformation of the tissue sample’s 
components may not be considered sufficiently 
“central to the purpose of the claimed process,” Bilski, 
545 F.3d at 962, because the transformation is 
incidental to the purpose of generating diagnostic 
information. Moreover, the jeopardy and uncertainty 
created by Bilski will upset the settled expectations of 
21 Although the Examiner indicated that addition of an 
assay would overcome the transformation-based rejection, see 
180 Office Action, p. 4, the addition could well be insufficient in 
view of the statement in the majority opinion below that “the 
transformation must be central  to the purpose of the claimed 
process.” Bilski, 545 F.3d at 962. 

those who, in obtaining patents for claims that may 
now run afoul of the machine-or-transformation test, 
followed the law as it existed at the time of the patent 
application.  See Festo v. Shoketsu Kinzoku Kogyo 
Kabushiki Co., 535 U.S. 722, 724 (2002) (“ ‘[C]ourts 
must be cautious before adopting changes that will 
disrupt the settled expectations of the inventing 
community.’ ” (citation omitted));22  see also Payne v. 
22 The Festo Court explained: 
    The responsibility for changing [settled law] rests 
with Congress. . . . Fundamental alterations in these 
rules risk destroying the legitimate expectations of 
inventors in their property. The petitioner in Warner-
Jenkinson  requested another bright-line rule . . . at 
the cost of disrupting the expectations of countless 
existing patent holders. We rejected that approach: 
“To change so substantially the rules of the game now 
could very well subvert the various balances the PTO 
sought to strike when issuing the numerous patents 
which have not yet expired and which would be 
affected by our decision.” [Warner-Jenkinson Co. v. 
Hilton Davis Chemical Co., 520 U.S. 17, 32 n.6 (1997)]; 
see also id.,  at 41, 117 S.Ct. 1040 (GINSBURG, J., 
concurring) (“The new presumption, if applied 
woodenly, might in some instances unfairly discount 
the expectations of a patentee who had no notice at 
the time of patent prosecution that such a presumption 
would apply”). As Warner-Jenkinson recognized, patent 
prosecution occurs in the light of our case law. 
Inventors who amended their claims under the 
previous regime had no reason to believe they were 
conceding all equivalents. If they had known, they 
might have appealed the rejection instead. There is no 
justification for applying a new and more robust 
estoppel to those who relied on prior doctrine. 
Festo, 535 U.S. at 739. 

Tennessee,  501 U.S. 808, 828 (1991) (adhering to 
established law, and to consequently settled expecta-
tions, is particularly important “in cases involving 
property and contract rights, where reliance interests 
are involved”); Bilski, 545 F.3d at 977, 993 (Newman, 
J., dissenting). Some of the more well-known 
examples of patents now in danger include:  
Prognosis for Colon Cancer: Claim 9 
of U.S. Patent No. 7,163,801 assigned to 
National Institutes of Health, U.S. Dept. 
of Health and Human Services, is 
directed to a method of determining a 
prognosis for survival for colon cancer in 
a patient having stage II colon carci-
noma by measuring levels of a bio-
marker in a colon cancer cell-containing 
sample: “A method of determining a 
prognosis for survival for a colon cancer 
patient having stage II colon carcinoma, 
comprising: (a) measuring levels of 
TUCAN polypeptide and one or more 
biomarker polypeptides selected from 
the group consisting of cIAP2, Apaf1, 
Bcl-2 and Smac in a colon cancer cell-
containing sample from said colon 
cancer patient, and (b) comparing the 
level of TUCAN polypeptide and the one 
or more selected biomarker polypeptides 
in said sample to a reference level of 
TUCAN polypeptide and said one or 
more selected biomarker polypeptides 
from normal colon tissue, wherein a 
lower level of TUCAN polypeptide and a 
higher level of any of Apaf1, Bcl-2, or 

Smac, or a lower level of TUCAN 
polypeptide and a lower level of cIAP2 in 
said sample relative to said reference 
level correlate with increased survival of 
said patient.” 
Colon Neoplasia Detection: Claim 13 
of U.S. Patent No. 7,485,420, assigned 
on its face to Case Western Reserve 
University, identifies a method com-
prising determining the likelihood that a 
human subject has colon neoplasia by 
detecting a vimentin expression level 
relative to a control: “A method for 
detecting the likelihood that a human 
subject has colon neoplasia, comprising 
detecting vimentin protein or nucleic 
acid expression level in a sample from 
the human subject, wherein reduced 
expression level of vimentin protein or 
nucleic acid relative to a control sample 
from a healthy subject is indicative of 
the likelihood that the human subject 
has colon neoplasia.” 
•  Prostate Specific Antigen (“PSA”) 
test for prostate cancer: Claim 10 of 
U.S. Patent No. 5,840,501, assigned on 
its face to Bayer Corp., identifies a 
method consisting of any immunoassays 
followed by a correlation: “A method for 
monitoring the course of disease in a 
male patient diagnosed with prostate 
cancer, comprising the performance of 
a series of immunoassays over time to 
determine changes in the level of 

complexed prostate specific antigen 
(cPSA) in blood samples obtained from 
such patient, whereby changes in the 
cPSA blood level correlate with changes 
in disease status.” PSA is widely used to 
diagnose prostate cancer. 
•  Test for HIV/AIDS: Claim 1 of U.S. 
Patent No. RE38352, assigned on its 
face to Stanford University, identifies a 
method consisting of any test for a 
specific nucleic acid mutation, followed 
by a correlation: “A method of evaluating 
the effectiveness of antiretroviral 
therapy of an HIV-infected patient 
comprising: collecting a plasma sample 
from an HIV-infected patient; and 
determining whether the plasma sample 
comprises nucleic acid encoding HIV 
reverse transcriptase having a mutation 
at codon 215, in which the presence of 
the mutation correlates positively with 
an accelerated immunologic decline of 
said patient compared to patients who 
do not have the mutation.” Mutations 
in the HIV virus within an infected 
individual are widely used to help people 
find and take drugs that will make them 
better, and to avoid drugs that will make 
them sicker. 
•  HER-2/neu test for breast and 
ovarian cancer: Claim 1 of U.S. Patent 
No. 4,968,603, assigned on its face to the 
University of California, identifies a 
method consisting of any test for the 

amplification level of the HER-2/neu 
gene, followed by classifying an in-
creased amplification relative to a refer-
ence level: “A method for screening 
patients to determine disease status, 
said method comprising: measuring the 
level of amplification or expression of the 
HER-2/neu gene in a sample from a 
patient suffering from breast or ovarian 
adenocarcinoma; and classifying those 
patients having an increased level of 
amplification or expression of the HER-
2/neu gene relative to a reference level 
characteristic of normal cells as being 
more likely to suffer disease relapse or 
having a decreased chance of survival.” 
HER-2/neu-related tests are widely used 
to determine which drug should be taken 
by a breast cancer patient. 
•  Test for neoplastic (i.e., cancerous) 
tissue:  Claim 7 of U.S. Patent No. 
5,955,263, assigned on its face to Johns 
Hopkins University and Genzyme Corp., 
identifies a method consisting of com-
paring normal and abnormal proteins, 
and detecting a mutation-based altera-
tion in the amino acid sequence wherein 
the alteration indicates neoplasia: “A 
method to aid in determining neoplasia 
of a tissue of a human, comprising: 
comparing (a) p53 proteins in a human 
tissue suspected of being neoplastic to 
(b) wild-type p53 proteins in a normal 
tissue of said human; detecting an 
alteration in the amino acid sequence 

between the p53 proteins, wherein the 
alteration is due to a mutation in a p53 
gene in the human tissue suspected of 
being neoplastic, wherein the mutation 
is selected from the group consisting of: 
a point, deletion, missense, and frame-
shift mutation, wherein an alteration 
in the amino acid sequence indicates 
neoplasia.” Science Magazine named p53 
the “molecule of the year.” Mutations in 
p53 help doctors determine whether a 
tissue is cancerous. 
The repercussions for the future of biotechnology, 
particularly diagnostics, if the decision below is 
affirmed would be staggering. The health care 
industry relies on the economic incentives provided 
by our patent system, including in large part by the 
patentability of diagnostic method claims. If such 
claims were subject to invalidation as unpatentable, 
health care companies would lose incentive to conduct 
research into basic diagnostics, to develop 
personalized medicine tools and diagnostic systems, 
to validate them, and to have them approved by the 
FDA – all steps that are tremendously costly and 
necessary for the public to derive any benefit from 
new diagnostics. Likewise, venture capitalists, 
financial firms, and established companies would no 
longer have incentives to fund or invest in health care 
companies that pursue the research, development, 
and regulatory approval of drugs and diagnostic 
systems. If there is no expectation of a limited right 
to exclusivity, industry will respond: These areas will 

be neglected in favor of other areas for which patent 
protection is still available.23  
Weighty policy issues underlie our carefully 
structured and long-standing patent system. While 
the decision below would change this framework and 
impose a further, rigid limitation on patentability, 
Harm from declaring diagnostic method claims 
unpatentable is not limited to the loss of incentives for research 
and development. Rather, the diagnostics segment of the 
biotechnology industry – which industry in 2008 generated 
about $70 billion in revenues, employed 190,000 people, and had 
a market capitalization of more than $340 billion – could be 
seriously jeopardized. See Glen T. Giovannetti & G. Jaggi, Ernst 
& Young, Beyond Borders – Global Biotechnology Report 2009, p. 
34G (2009). As discussed above, an affirmance here could cause 
numerous two-step diagnostic patents to be rendered void. At a 
minimum, companies holding those patents – and their 
investors and financial backers – would face uncertainty as to 
the value of their patents and the corresponding value of their 
businesses. It is unquestionable that a biotechnology company’s 
value drops precipitously upon expiration of its patents, 
demonstrating the economic value afforded by patent protection. 
For example, in anticipation of the expiration of its patent on 
the cholesterol drug Zocor in June 2006, Merck announced in 
December 2005 that it expected sales of Zocor to drop from $4.35 
billion in 2005 to $2.45 billion in 2006. See  Merck Plans More 
Cost-Cutting, N.Y. TIMES, Dec. 16, 2005, at C5. In 2007, as a 
result of generic competition, Merck’s sales of Zocor were only 
$877 million. See  Gina-Louise Monari, Pressure rises in cardio, 
MedAd News, Feb. 2009, available at http://www.pharmalive. 
com/magazines/medad/view.cfm?articleID=7173. Any ruling that 
would render diagnostic method claims unpatentable would 
hasten such reduction of value for numerous companies, with 
devastating effects for the biotechnology industry.  

any such revision should be left to the Legislative 
branch. This Court so stated in Chakrabarty:  
The choice we are urged to make is a matter 
of high policy for resolution within the 
legislative process after the kind of 
investigation, examination, and study that 
legislative bodies can provide and courts 
cannot. That process involves the balancing 
of competing values and interests, which in 
our democratic system is the business of 
elected representatives. Whatever their 
validity, the contentions now pressed on us 
should be addressed to the political branches 
of the Government, the Congress and the 
Executive, not to the courts. 
447 U.S. at 317; see Diehr, 450 U.S. at 182.24 In sum, 
any ruling in this case should not upset settled law 
and expectations concerning the scope of patent-
----------------- ♦ ----------------- 
24 Congress can and does amend the patent law when it 
finds that a change is in the public interest. For example, in 
1996, Congress exempted certain medical activity from giving 
rise to infringement liability. 35 U.S.C. § 287(c) (added by Pub. 
L. No. 104-208, § 616, 110 Stat. 3009, 3009-67 (Sept. 30, 1996)).  

The judgment of the Federal Circuit should be 
reversed insofar as it held the machine-or-
transformation test to be the exclusive test for pat-
entable subject matter in process claims. 
Respectfully submitted, 
  Counsel of Record 
1301 Avenue of the Americas, 
New York, NY 10019 
(212) 999-5800 
Attorneys for Amicus Curiae 
  Caris Diagnostics, Inc. 

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