No. 08-964 
In The 
Supreme Court of the United States 
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On Writ Of Certiorari To The 
United States Court Of Appeals 
For The Federal Circuit 
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  Counsel of Record 
345 Oyster Point Blvd. 
South San Francisco, CA 94080
(650) 624-4198 
801 California Street 
301 Penobscot Drive 
Mountain View, CA 94041 
Redwood City, CA 94063 
(650) 988-8500 
(650) 556-9300 
Counsel for Amici Curiae 
OR CALL COLLECT (402) 342-2831 

1.  Whether the Federal Circuit erred by holding 
that a “process” must be tied to a particular machine 
or apparatus, or transform a particular article into a 
different state or thing (“machine-or-transformation” 
test), to be eligible for patenting under 35 U.S.C. 
§ 101, despite this Court’s precedent declining to limit 
the broad statutory grant of patent eligibility for 
“any” new and useful process beyond excluding 
patents for “laws of nature, physical phenomena, and 
abstract ideas.” 
2. Whether the Federal Circuit’s “machine-or-
transformation” test for patent eligibility, which 
effectively forecloses meaningful patent protection to 
many business methods, contradicts the clear 
Congressional intent that patents protect “method[s] 
of doing or conducting business.” 35 U.S.C. § 273. 

INTEREST OF THE AMICI CURIAE ...................  

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

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


A.   The Federal Circuit Erred In Holding 
That A “Process” Must Be Tied To A 
Particular Machine Or Apparatus, Or 
Transform A Particular Article Into A 
Different State Or Thing (“Machine-
Or-Transformation” Test), To Be Eligi-
ble For Patenting Under 35 U.S.C. 
§ 101 .......................................................  10 
The Machine-Or-Transformation Test 
Does Not Properly Distinguish Be-
tween Patent-Eligible And Patent-
Ineligible Subject Matter ......................   12 
The Machine-Or-Transformation Test 
Is Inconsistent With 35 U.S.C. § 101 
And This Court’s Long-Standing Prec-
edent ......................................................   13 

MATTER ......................................................   15 
A.    This Court Should Determine Whether 
A Law Of Nature, Natural Phenom-
enon Or Abstract Idea Is Claimed And 
Construe Those Terms In The Ordi-
nary English Sense ................................   15 
B.    Diagnostic  Claims Drawn To Methods 
Of Predicting Response In A Patient Are 
Patent-Eligible Because They Do Not 
Describe A Fundamental Principle .........   21 
Personalized Medicine Is A Growing 
Field With A Tremendous Potential To 
Help Patients .........................................   26 
B.   Because The Machine-Or-Transformation 
Test Endangers Funding For Person-
alized Medicine Companies, It Will 
Undermine Personalized Medicine Com-
panies, Stifle Development And Ulti-
mately Harm Patients ...........................    31 
CONCLUSION .......................................................   33 

Arrhythmia Research Technology,  Inc. v. 
Corazonix Corp., 958 F.2d 1053 (Fed. Cir. 
1992) ........................................................................ 11 
Classen Immunotherapies, Inc. v. Biogen IDEC
381 F. Supp. 2d 452 (D. Md. 2005), aff ’d
2008 U.S. App. LEXIS 25661 (Fed. Cir. Dec. 
19, 2008) .................................................................. 24 
Cochrane v. Deener, 94 U.S. 780 (1876) ....................... 8 
Diamond v. Chakrabarty, 447 U.S. 303 (1980).......... 14 
Diamond v. Diehr, 450 U.S. 175 (1981) ................. passim 
Funk Brothers Seed Co. v. Kalo Inoculant Co., 
333 U.S. 127 (1948) ........................................... 16, 25 
Gottschalk v. Benson, 409 U.S. 63 (1972) .......... passim 
In re Bilski, 545 F.3d 943 (Fed. Cir. 2008) ......... passim 
In re Nuijten, 500 F.3d 1346 (Fed. Cir. 2007) ............ 11 
Jacobellis v. Ohio, 378 U.S. 184 (1964) ..................... 16 
KSR Int’l Co. v. Teleflex,  Inc., 550 U.S. 398 
(2007) ....................................................................... 14 
Laboratory Corp. of Am. Holdings v. Metabolite 
Labs. Inc., 548 U.S. 124 (2006) ................... 21, 24, 31 
Parker v. Flook, 437 U.S. 584 (1978) ................. passim 
Perrin v. United States, 444 U.S. 37 (1979) ............... 16 
Prometheus Labs. v. Mayo Collaborative Servs.
2008 U.S. Dist. LEXIS 25062 (S.D. Cal. Mar. 
28, 2008) .................................................................. 24 

Shepard v. United States, 544 U.S. 13 (2005) ........... 13 
State Street  Bank & Trust Co. v. Signature 
Financial Group, Inc., 149 F.3d 1368 (Fed. 
Cir. 1998) ................................................................. 12 
Waxham v. Smith et al., 294 U.S. 20 (1935) ................ 8 
35 U.S.C. § 100(b) ......................................................... 6 
35 U.S.C. § 101 ................................................... passim 
35 U.S.C. § 103 ........................................................... 14 
35 U.S.C. § 273 ............................................................. 7 
Supreme Court Rule 37 ................................................ 1 
145 Congressional Record H11769 (daily ed. 
Nov. 9, 1999) .............................................................. 7 
Julie E. Cohen and Mark A. Lemley, Patent 
Scope and Innovation in the Software 
Industry, 89 Cal. L. Rev. 1 (2001) ........................... 12 
Genomics and Personalized Medicine Act of 
2006 ......................................................................... 30 

C. Kongkaew, et al., Hospital admissions 
associated with adverse drug reactions, Ann 
Pharmacother 42(7):1017-1025 (2008) ................... 27 
Oxford English Dictionary 6 (2d ed. 1989) ... 6, 7, 17, 18 
B. Spear, et al., Clinical application of pharma-
cogenomics, Trends Mol. Med. 7(5):201-204 
(2001) ....................................................................... 26 

Personalized medicine is universally acknowl-
edged to hold enormous potential for treating 
diseases, improving the quality of patients’ lives and 
streamlining the drug discovery and development 
process. Personalized medicine uses molecular diag-
nostic tests to correlate genetic and molecular 
biomarkers with clinically useful disease charac-
teristics. The technology has already delivered 
tremendous results for individual patients, and 
current research efforts and clinical trials promise 
significant future improvements in health care. 
Personalized medicine companies are typically 
small and rely on private investment capital to sus-
tain them through the lengthy and expensive re-
search, development and commercialization process. 
Developing the tests is time consuming and ex-
pensive. Personalized medicine companies literally 
flourish or fail based on their ability to build patent 
portfolios protecting diagnostic correlations. 
The success of personalized medicine in the 
diagnosis and treatment of breast cancer has been 
unexpectedly spectacular. Modern sophisticated mo-
lecular diagnostic tests allow providers to identify the 
1 In accordance with Sup. Ct. R. 37, the Amici state that 
this brief was not authored in whole or in part by counsel to a 
party, and that no monetary contribution to the preparation or 
submission of this brief was made by any person or entity other 
than these Amici Curiae or their counsel. 

30% of patients who have breast cancer tumors that 
over-express human epidermal growth factor receptor 
2 (HER2). These patients can be treated with 
trastuzumab, an antibody that is more effective and 
less toxic than traditional chemotherapy or radiation 
Monogram Biosciences, Inc. and Genomic Health, 
Inc. are publically traded companies recognized as 
world leaders in the emerging field of personalized 
medicine. Monogram Biosciences currently offers the 
HERmark® breast cancer diagnostic assay that accu-
rately quantifies HER2. HERmark® identifies pa-
tients likely to respond to trastuzumab with greater 
precision than currently available tests. In addition, 
Monogram offers five distinct HIV drug resistance 
assays used to individualize the selection of antivirals 
for HIV treatment. Monogram’s HIV assays provide a 
direct measure of the patient’s virus’ ability to survive 
in the presence of specific antiviral drugs and are 
often the primary tests relied on by physicians to 
determine which HIV drugs will be effective in a 
specific patient.  
Genomic Health currently offers the Oncotype 
DX® assay that provides information on the 
likelihood that a breast cancer patient will experience 
(1) a recurrence of a tumor; and (2) a clinically 
beneficial response to chemotherapy. In addition, 
Genomic Health has completed validation of a colon 
cancer prognostic assay which it expects to offer com-
mercially in 2010. 

Amici is their ability to obtain 
meaningful proprietary protection for their key 
discoveries: diagnostic correlations. Amici expend 
tremendous resources in obtaining tumor samples, 
assaying the samples to discover correlations and 
searching through and analyzing the results for 
meaningful statistical significance that could identify 
those correlations. There are literally hundreds of 
unsuccessful attempts made for each identified 
Amici have an interest in ensuring that patent 
claims to the discovered diagnostic correlations 
remain patentable. Amici would have difficulty 
in continuing with their mission of developing prod-
ucts for patients in the absence of meaningful patent 
protection. The application of the machine-or-
transformation test as adopted by the Federal Circuit 
to the diagnostic correlations forecloses the ability of 
Amici to obtain commercially meaningful protection 
for its discovery and products, and threatens the 
future of the entire field of personalized medicine. 
Patients can only suffer. 
Amici will focus on the first question presented 
as it relates to correlation claims often sought by 
personalized medicine companies. 
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The patent system creates incentives for research 
into discovering correlations between biomarkers and 

diseases to improve diagnostic tests thereby creating 
a virtuous cycle progressing science to the benefit of 
patients and society. The Federal Circuit’s require-
ment that all claims recite a “physical” step, such as a 
machine or physical transformation step, jeopardizes 
the future of research in personalized medicine 
by making many biologically-based inventions un-
patentable under 35 U.S.C. § 101. In the end, fewer 
personalized medicine avenues will be explored and 
brought to market, and patients will suffer.  
The Federal Circuit erred in holding that a 
process must be tied to a particular machine or 
apparatus or transform a particular article into a 
different state or thing to be eligible for patent 
protection under 35 U.S.C. § 101. The machine-or-
transformation test may work in a few cases for 
determining whether a particular claim is patent-
eligible, but it results in “false negatives” for the 
majority of cases. Specifically, it has been applied to 
find some claims, such as those on the actual 
diagnostic correlations, to be patent-ineligible. Amici 
urge the Court to adopt a framework for patent-
eligible subject matter that accords with the existing 
law, a framework that determines that non-physical 
processes are patent-eligible, a framework that will 
foster development of personalized medicine tech-
Consistent with this Court’s precedent, Amici 
propose that the Court articulate a framework that 
considers as a threshold step whether a fundamental 
principle (i.e., a law of nature, a phenomenon of 

nature or an abstract idea) is claimed. For application 
of the framework, the terms law of nature,  natural 
phenomenon and abstract idea should be construed in 
the ordinary English sense each as a universal 
principle having a central role in scientific practice 
and each as being fundamental. If a law of nature, 
natural phenomenon or abstract idea is not claimed, 
the claimed subject matter describes a patent-eligible 
process. If one of these is claimed, the Court should 
turn its attention to secondary considerations such 
as whether the patent claim entirely preempts 
the law of nature, natural phenomenon or abstract 
idea. Such a determination can take into account 
whether the claimed method involves a machine-or-
transformation step, but not as the sole deter-
minative test for patentability. Amici believe that 
once the Court sets forth a definitive test, the Court 
will determine that claim 1 in Bilski’s application is 
patent-eligible because it does not claim a law of 
nature, natural phenomenon or abstract idea. Simi-
larly, the claims important to personalized medicine 
companies, claims to the discovered correlations, will 
be patent-eligible since they also do not involve laws 
of nature, natural phenomena or abstract ideas. 
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35 U.S.C. § 101 provides the basis for patent-
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 
therefore, subject to the conditions and 
requirements of this title. 
The statute states that there are four separate and 
distinct categories of patentable subject matter, 
namely: 1) processes, 2) machines, 3) manufactures or 
4) compositions of matter. In addition, 35 U.S.C. 
§ 100(b) provides a broad statutory definition for a 
process to be used in 35 U.S.C. § 101: 
The term “process” means process, art, or 
method, and includes a new use of a known 
process, machine, manufacture, composition 
of matter, or material.2 
According to the Oxford English Dictionary, a 
“process” can be defined as: 
2 The statutory provision on what constitutes patentable 
subject matter has essentially been the same since 1793. Until 
the Patent Act of 1952, the patent statutes used the word “art.” 
The 1952 Act substituted the word “process.” To emphasize that 
no change of meaning was intended, a process was defined as 
“ . . . any process, art or method . . . ” 35 U.S.C. § 100(b). 

A continuous and regular action or suc-
cession of actions, taking place or carried on 
in a definite manner, and leading to the 
accomplishment of some result; a continuous 
operation or series of operations (The Oxford 
English Dictionary 6 (2d ed. 1989)). 
The term “process” thus does not have a special 
meaning that would exclude non-physical processes 
from patent eligibility under 35 U.S.C. § 101.  
Nor is there any basis for concluding that the 
Constitution imposes a requirement that non-
physical processes be excluded. According to this 
Court, Congress has the authority to include non-
physical subject matter within the scope of patent-
eligible subject matter.3 In the encompassing 
language as it used in § 101, Congress chose not to 
limit patentable subject matter to only physical 
subject matter; the only limitations are that the 
subject matter be “new and useful.”4  
3  See e.g.,  Gottschalk v. Benson, 409 U.S. 63, 72 (1972), 
where the Court stated, “It may be that the patent laws should 
be extended to cover these programs, a policy matter to which 
we are not competent to speak.” See also, 35 U.S.C. § 273 and 
145 Cong. Rec. H11769, at 11801 (daily ed. Nov. 9, 1999) (“Jt. 
Conf. Report”), where, in discussing Title 35, Congress expressed 
the intent that the patent laws may be drawn to physical as well 
as non-physical limitations. 
4 Other Amici extensively treat what it means for a process 
to be “useful.” Accordingly, this brief will not repeat such 
detailed analysis. 

This Court has consistently and explicitly 
refused to limit a process to the purely 
physical. In Gottschalk v. Benson, 409 U.S. 
63, 71 (1972), even as the Court was denying 
the patentability of a method of converting 
binary signals from one form to another, 
citing  Waxham v. Smith et al., 294 U.S. 20 
(1935), the Court could not have more clearly 
stated that a process need not have a 
machine-or-transformation, a physical step, 
to be patentable: 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. 
Gottschalk,  409 U.S. at 71. In Parker v. Flook, 437 
U.S. 548, 589 n.9 (1978),  the Court repeated and 
strengthened this rationale: 
The statutory definition of process is broad. 
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.” See  Cochrane v. Deener, 94 
U.S. 780, 787-788 (1876). As in Benson,  we 
assume that a valid process patent may issue 
even if it does not meet one of these qual-
ifications of our earlier precedents. (internal 
citations omitted) 

Accordingly, the Court has consistently made it clear 
that the process category of 35 U.S.C. § 101 should be 
interpreted broadly to include all subject matter, 
physical and non-physical.5 Other than the proscribed 
categories of laws of nature, phenomena of nature 
and abstract ideas (see, e.g., Gottschalk v. Benson, 409 
U.S. 63 (1972); Parker v. Flook, 437 U.S. 584 (1978) 
and Diamond v. Diehr, 450 U.S. 175 (1981)) all proc-
esses, both physical and non-physical, are patent-
Amici would urge this Court to hold that 
processes include all subject matter, physical and 
5 Congress has also expressed its intent that a process 
should include the physical as well as the non-physical. See, e.g., 
Jt. Conf. Report at 11801, where they indicate that they believe 
that a process is not limited to the physical but should also 
include the non-physical. 

A.  The Federal Circuit Erred In Holding 
That A “Process” Must Be Tied To A 
Particular Machine Or Apparatus, Or 
Transform A Particular Article Into A 
Different State Or Thing (“Machine-
Or-Transformation” Test), To Be Eligi-
ble For Patenting Under 35 U.S.C. § 101 
Despite admonitions from the Supreme Court, in 
Bilski, the Federal Circuit adopted the physical limi-
tation requirement of the machine-or-transformation 
test as the sole test, effectively denying patentability 
to much patent-eligible subject matter. Though the 
Federal Circuit adamantly denied that the machine-
or-transformation step required a physical step,6 the 
test it ultimately adopted clearly does require a 
physical step. In articulating the ‘transformation’ 
prong of the machine-or-transformation test, the 
Federal Circuit stated: 
Purported transformations or manipulations 
simply of public or private legal obligations 
or relationships, business risks, or other 
such abstractions cannot meet the test 
6  In re Bilski, 545 F.3d 945, 963 (2008), see id., at  964, 
where the Federal Circuit explicitly stated that it was rejecting 
any notion of a physical steps test. 

because they are not physical objects or 
substances, and they are not representative 
of  physical objects or substances.7 (emphasis 
Thus, the Federal Circuit adopts a physical test at 
the same time that it asserts that it is not adopting a 
physical test. 
  Patent-eligible subject matter has been 
traditionally limited only by whether the subject 
matter is directed to a law of nature, a phenomenon 
of nature or an abstract idea. Other than these 
traditional categories of patent-ineligible subject 
matter, the courts have been consistent in holding 
that process steps are patentable despite the fact that 
they lack a physical limitation, such as a machine-or-
transformation step.8 Indeed, attempting to distin-
guish between physical and non-physical steps will 
lead to a futile effort in metaphysics and invite 
practitioners to ‘game’ the system.9 Thus, the Federal 
7  In re Bilski, 545 F.3d at 963. 
8  See, e.g., Gottschalk v. Benson, 409 U.S. 63 (1972); Parker 
v. Flook, 437 U.S. 584 (1978) and Diamond v. Diehr, 450 U.S. 
175 (1981). 
9  See,  e.g.,  Arrhythmia Research Technology, Inc. v. 
Corazonix Corp., 958 F.2d 1053 (Fed. Cir. 1992), where the 
Federal Circuit found that the terms “determining” and “com-
paring” were physical process steps and that electrical signals 
were inherently physical and In re Nuijten, 500 F.3d 1346 (Fed. 
Cir. 2007), where the Federal Circuit determined that electrical 
signals, while physical, were too transitory to fall within one of 
the statutory categories for patentable subject matter. It is 
unclear why the “transitory” nature of a signal is problematic, 
(Continued on following page) 

Circuit erred in holding that a process must be tied to 
a particular machine or apparatus, or transform a 
particular article into a different state or thing. 
B. The Machine-Or-Transformation Test 
Does Not Properly Distinguish Be-
tween Patent-Eligible And Patent-
Ineligible Subject Matter 
There is quite a bit of patentable ground between 
a process that is not limited by a physical step, such 
as a machine-or-transformation step, and a process 
that is. The machine-or-transformation test, by 
requiring a physical limitation in the claims, 
classifies all physical processes as patent-eligible 
subject matter but misses much non-physical patent-
eligible subject matter that is acceptable under this 
Court’s precedent. Namely, the test fails to identify 
non-physical subject matter which is not a law of 
nature, natural phenomenon or an abstract idea. As 
an example, as Amici will discuss in section III(B) 
below, claim 13 of U.S. Patent No. 4,940,658 (“ ’658”) 
since many physical phenomena, such as chemical processes, are 
equally transitory, but unquestionably patentable. See also State 
Street Bank & Trust Co. v. Signature Financial Group, Inc., 149 
F.3d 1368 (Fed. Cir. 1998), where the transitory nature of the 
calculated net asset value was not a bar to patent eligibility. As 
far as “gaming” the system, a clever patent practitioner will be 
able to say the so-called “magic words” so that a claimed inven-
tion is drawn to some sort of a machine or has a physical trans-
formation step. See Julie E. Cohen and Mark A. Lemley, Patent 
Scope and Innovation in the Software Industry, 89 Cal. L. Rev. 1 

patent claims non-physical subject matter which is 
not a law of nature, natural phenomenon or an 
abstract idea. 
Thus, the machine-or-transformation test does 
not adequately distinguish between patent-eligible 
and patent-ineligible subject matter. 
C.  The Machine-Or-Transformation Test Is 
Inconsistent With 35 U.S.C. § 101 And 
This Court’s Long-Standing Precedent 
The Federal Circuit erred in In re Bilski by creat-
ing a new and amorphous “machine-or-transformation” 
test that is inconsistent with 35 U.S.C. § 101 and 
long-standing Supreme Court precedent. As noted in 
the dissenting opinions in Bilski, the majority’s novel 
test raises more questions than it answers, and 
indeed creates significant confusion. The Federal 
Circuit’s interpretation of 35 U.S.C. § 101 uprooted 
years of case law, which should only be done for the 
most compelling reasons. “Considerations of stare 
decisis have special force in the area of statutory 
interpretation, for here, unlike in the context of 
constitutional interpretation, the legislative power is 
implicated, and Congress remains free to alter what 
[the courts] have done.” Shepard v. United States
544 U.S. 13, 23 (2005). “Where, as here, Congress has 
not acted to modify the statute in the many years 
since Diehr and the decisions of [the Federal Circuit], 
the force of stare decisis is even stronger.” In re Bilski
545 F.3d at 993 (Newman, J., dissenting) (citing 
Shepard, 544 U.S. at 23). The Federal Circuit’s 

majority decision in Bilski is based on a misguided 
and novel reading of selected Supreme Court 
quotations; it disrupts both settled precedent and 
long-standing expectations concerning intellectual 
property rights, and is bad public policy. 
Recent Supreme Court precedent calls for judicial 
flexibility in carrying out the Constitutional and 
statutory mandates of the patent system. Indeed, the 
Supreme Court recently rejected rigid Federal Circuit 
precedent in KSR Int’l Co. v. Teleflex, Inc., 550 U.S. 
398 (2007), when it overruled the “teaching, sug-
gestion, or motivation,” or TSM, test for analyzing 
obviousness under 35 U.S.C. § 103. While recognizing 
that the TSM test was developed to “resolve the 
question of obviousness with more uniformity and 
consistency,” the Supreme Court summarily rejected 
the overly-rigid rule as “contrary to §103 and [its] 
precedents.”  Id. at 407. Unfortunately, the machine-
or-transformation test similarly seeks to achieve 
consistency and predictability by supplanting the 
broad and flexible Supreme Court precedent 
governing patentability under § 101 (see Diehr, 450 
U.S. at 185; Diamond v. Chakrabarty, 447 U.S. 303, 
309 (1980); and Benson, 409 U.S. at 93), with a 
narrow and rigid test. As KSR demonstrates, such an 
effort to achieve predictability, even if well-intended, 
is not reason enough to disregard controlling 

A.  This Court Should Determine Whether 
A Law Of Nature, Natural Phenom-
enon Or Abstract Idea Is Claimed And 
Construe Those Terms In The Ordi-
nary English Sense 
Amici propose a framework that considers as a 
threshold step whether a fundamental principle (i.e., 
a law of nature, a phenomenon of nature or an 
abstract idea) is claimed. If not, the claimed subject 
matter describes a patent-eligible process. If a 
fundamental principle is claimed, the patent claim 
should be analyzed to determine if it entirely 
preempts the fundamental principle. Such a deter-
mination can take into account whether the claimed 
method involves a machine-or-transformation step, 
but not as the sole determinative test for pat-
entability. For application of the test, the terms law of 
naturenatural phenomenon and abstract idea should 
be construed in the ordinary English sense as 
universal having a central role in scientific practice 
and as being fundamental. 
As a threshold for the determination of whether 
patent-eligible subject matter is present, Amici 
propose an investigation of the ordinary English 
meaning of the words law of nature, natural 

phenomenon and abstract idea.10 Amici would propose 
that the Court adopt a workable definition for each of 
those terms which could be rationally applied by 
practitioners.11 Consistent with the Court’s trend 
towards reading words in an ordinary English way,12 
10 Courts have never determined what exactly is included 
within the terms “law of nature, natural phenomenon and 
abstract idea” by construing the boundaries of those terms to 
determine whether they do, in fact, have one of these 
fundamental principles before them (see,  e.g.,  Funk Brothers 
Seed Co.  v. Kalo Inoculant Co., 333 U.S. 127, 130 (1948) 
(determining that bacterial qualities of non-inhibition were 
phenomena of nature); Flook, 437 U.S. at 595 (determining that 
a method of calculating is drawn to non-statutory subject 
matter);  Gottschalk, 409 U.S. at 68 (holding that a method of 
binary conversion was so abstract as to not be patentable); 
Diehr, 450 U.S. at 191 (holding that a claim to a process for 
curing rubber which employed a mathematical equation did not 
only entail an abstract mathematical formula and thus was 
drawn to patentable subject matter). Amici believe that such an 
approach, a sort of “ . . . know it when I see it . . . ” approach (see 
Justice Potter Stewart’s statement in his concurrence in 
Jacobellis v. Ohio, 378 U.S. 184 (1964) for example) has led to 
much confusion. Amici  do  note  that  some  justices  of  the 
Supreme Court have cautioned against trying to define such 
concepts as a law of nature, natural phenomenon or abstract 
idea (see,  e.g.,  Funk Brothers Seed Co., 333 U.S. at 133 
(Frankfurter, J., concurring). But, we believe that a rational, 
perhaps flexible, definition would be the best way to make the 
process and analysis more meaningful. 
11  Amici realize that the Courts have also been disposed to 
consider thinking as patent ineligible. Amici believe the Court 
should also adopt a position that claim language should be 
construed, when possible, to avoid implicating the process of 
thinking. The proposal is set forth below. 
12  See, e.g.Perrin v. United States, 444 U.S. 37, 42 (1979). 

Amici propose that each of the terms “law of nature, 
natural phenomenon and abstract idea” should 
incorporate the following elements: 
1.  That they are universal as defined in 
terms of ordinary English and thus have 
a central role in scientific practice; and 
2.  That they are fundamental, as defined 
in terms of ordinary English. 
For the terms “universal” and “fundamental,” Amici 
would propose that the Court adopt the following 
A. Universal: 
Something which is an absolute or general 
concept regarded either as forming or having 
an absolute, mental or nominal existence; a 
universal proposition; a general term, notion 
or idea. (The Oxford English Dictionary (2d 
ed. 1989)) 
B. Fundamental: 
Something which is a leading or primary 
principle, rule, law, or article which serves as 
the groundwork of a system; an essential 
part. (The Oxford English Dictionary (2d ed. 

For the terms “law of nature”, “phenomenon”, and 
“abstract”, we would propose the following defini-
C.  Law of Nature: 
In the sciences of observation, a theoretical 
principle deduced from particular facts, 
applicable to a defined group or class of 
phenomena, and expressible by the state-
ment that a particular phenomenon always 
occurs if certain conditions are present. (The 
Oxford English Dictionary (2d ed. 1989)) 
D. Phenomenon: 
In scientific and general use, a thing that 
appears, or is perceived or observed; an 
individual fact, occurrence, or change as 
perceived by any of the senses, or by the 
mind; applied chiefly to fact or occurrence, 
the cause or explanation of which is in 
question. (The Oxford English Dictionary (2d 
ed. 1989)) 
E. Abstract: 
Refers to something that is withdrawn or 
separated from material embodiment, from 
practice, or from particular examples. Thus, 
an abstract idea is an idea that is withdrawn 
or separated from material embodiment, 
from practice, or from particular examples. 
(The Oxford English Dictionary (2d ed. 

Accordingly, consistent with this Court’s precedent,13 
Amici would propose that the terms “law of nature,” 
“natural phenomenon” and “abstract idea” should be 
defined as follows: 
A.  Law of Nature 
A law of nature is, in the sciences of 
observation, a theoretical principle deduced 
from particular facts, applicable to a defined 
group or class of phenomena, and expressible 
by the statement that a particular phenom-
ena always occurs if certain conditions are 
present. A law of nature has an absolute or 
general concept regarded either as forming 
or having an absolute, mental or nominal 
existence; a universal proposition; a general 
term, notion or idea. A law of nature is also a 
leading or primary principle, rule, law or 
article which serves as the groundwork of a 
system, an essential part. 
B. Phenomenon 
A phenomenon of nature appears, or is 
perceived or observed; an individual fact, 
13  See, e.g.Gottschalk v. Benson, 409 U.S. 63 (1972); Parker 
v. Flook, 437 U.S. 584 (1978); and Diamond v. Diehr, 450 U.S. 
175 (1981), where this Court has consistently justified the 
exclusion of patent-ineligible categories on the supposition that 
they were fundamental principles, those containing a funda-
mental truth, an original cause, a motive, the basic tools of 
scientific research, part of the storehouse of knowledge available 
to all. Thus any set of working definitions should include these 

occurrence, or change as perceived by any of 
the senses, or by the mind; applied chiefly to 
fact or occurrence. A phenomenon of nature 
has an absolute or general concept regarded 
either as forming or having an absolute or 
nominal existence; a universal proposition. A 
phenomenon of nature is also a leading or 
primary principle which serves as the 
groundwork of a system, an essential part. 
C. Abstract 
An abstract idea is an idea that is withdrawn 
or separated from material embodiment, 
from practice, or from particular examples. 
An abstract idea has an absolute or general 
concept regarded either as forming or having 
an absolute, mental or nominal existence; a 
universal proposition; a general term, notion 
or idea. An abstract idea is also a leading or 
primary principle which serves as the 
groundwork of a system, an essential part. 
To determine whether claimed subject matter is 
patent eligible, Amici propose this test with defini-
tions in mind: 
1.  As a threshold step, determine whether 
a fundamental principle (i.e., a law of 
nature, a phenomenon of nature or an 
abstract idea) is claimed. If not, the 
claimed subject matter describes a 
patent-eligible process. 
2.  If a fundamental principle is claimed, 
determine whether the patent claim 

entirely preempts the fundamental 
principle. The determination may take 
into account whether the claimed 
method involves a machine-or-trans-
formation step. If the claim does not 
entirely preempt the fundamental prin-
ciple, then it claims patent-eligible 
subject matter; if the claim does entirely 
preempt the fundamental principle, then 
it does not claim patent-eligible subject 
With this test and these definitions in mind, Amici 
now turn to a representative diagnostic claim, claim 
13 of U.S. Patent No. 4,940,658. 
B.  Diagnostic Claims Drawn To Methods 
Of Predicting Response In A Patient 
Are Patent-Eligible Because They Do 
Not Describe A Fundamental Principle 
Amici will focus on how the machine-or-
transformation test could affect personalized 
medicine companies, and claim 13 of U.S. Patent No. 
4,940,658, the claim that was the subject matter of 
Laboratory Corp. of Am. Holdings v. Metabolite Labs. 
Inc., 548 U.S. 124 (2006), provides an excellent 
vehicle to exemplify application of the proposed 
framework.14 The claim is directed to a non-physical 
14  Claim 13 recites: “A method for detecting a deficiency of 
cobalamin or folate in warm-blooded animals comprising the 
steps of: assaying a body fluid for an elevated level of total 
(Continued on following page) 

process, but non-physical processes are patentable, as 
So, as a first step, the Court should consider 
whether the process of correlating is drawn to a law 
of nature, a natural phenomenon or abstract idea, as 
Amici have defined these terms. Under the proposed 
test, the ordinary English meaning of the words 
“natural phenomenon” requires that the claimed 
assay be universal and have a central role in 
scientific practice. The scientific correlation of 
homocysteine levels with a deficiency of cobalamin 
describes a very narrow biological correlation, cer-
tainly not something universal and central to 
scientific practice.16 In the human body, many 
biological components, genes, proteins, tissues and 
even entire organs, work together through very 
complicated processes. Although the processes are 
connected, they are very different, and, indeed, a 
homocysteine; and correlating an elevated level of total 
homocysteine in said body fluid with a deficiency of cobalimin or 
15  One could argue that the “assaying” step, among others, 
does indeed require some sort of a physical step and requires a 
machine, as a result. Amicus have chosen to focus on the issue 
at hand, namely the “correlating” aspect of claim 13, and assume 
that the step does not require an assay step. 
16  Were one to analogize claim 13 to the Benson and Flook 
claims, the difference would be that the claims in Benson and 
Flook were, according to the Court, to the algorithm, per se
Claim 13, on the other hand, is drawn to a very narrow 
biological correlation. In any case, Amici would urge the Court 
to use extreme caution in completely analogizing biological 
claims to algorithm claims. 

single disease or disorder can often be associated with 
many different biomarkers in many different bio-
logical pathways. With so many different possible 
markers, even for the same disease, a patent 
monopoly on any one marker would not preclude 
scientists from discovering other pathways. 
Indeed, the patent monopoly provided by claim 
13 (or any claimed biological correlation) would not 
stifle innovation but would rather motivate others to 
seek out similar correlations, perhaps even in related 
biological pathways. Thus, claim 13 would not block 
the basic tools of research but would foster research. 
Similarly, in the specification of the ’658 patent, the 
diagnostic process is explained in great detail, 
including how the claimed correlation would be 
applied to specific testing subjects, each of these 
details show that the correlation is not universal and 
central to the scientific process. 
Under the proposed test, the ordinary English 
meaning of the words “natural phenomenon” require 
that the claimed assay additionally be fundamental, 
thus a leading or primary principle, rule, law or 
article which serves as the groundwork of a system, 
i.e. an essential part. The correlation exists in some 
human beings, perhaps as a product of evolution, and 
as such, it could have been different. And, if it could 
have been different, as evolution could have taken a 
different path, it does not describe a leading or 
primary principle, just an artifact of evolution. This is 
key: the fact that it could have been different 
demonstrates that it is not the groundwork for a 

system or an essential part. As a result, claim 13, as a 
correlation is not a fundamental principle and thus 
does describe patent-eligible subject matter.17 
In contrast, examples such as E=mc2, Newton’s 
law of gravity, and phenomena of nature such as 
water freezing or the aurora borealis would certainly 
constitute laws of nature and natural phenomena in 
the ordinary English meaning of the word. They each 
describe an absolute or general concept regarded as 
forming or having an absolute existence, and they are 
each universal and central to scientific practice. Each 
of these phenomena, and the principles behind them, 
could also be considered as the groundwork of a 
system, essential and fundamental, in other words. 
Each of these principles, unlike claim 13 in Lab. 
Corp. of Am. Holdings, very clearly fall into the 
category of a fundamental principle and would be the 
sort of patent-ineligible subject matter that would 
constitute the basic tools of research, the common 
knowledge of all. 
17  Amici believe this argument can be extended to the 
subject matter of all diagnostic claims. As examples, please see 
the claims in U.S. Patent No. 6,680,302 drawn to methods of 
optimizing therapeutic efficiency, the subject of Prometheus 
Labs. v. Mayo Collaborative Servs., 2008 U.S. Dist. LEXIS 25062 
(S.D. Cal. Mar. 28, 2008), as well as the claims in U.S. Patent 
No. 5,723,283, claims drawn to a method of determining 
whether an immunization schedule affects the incidence or 
severity of a chronic immune-mediated disorder, the subject 
matter of Classen Immunotherapies, Inc. v. Biogen IDEC, 381 
F. Supp. 2d 452 (D. Md. 2005), aff ’ d,  2008 U.S. App. LEXIS 
25661 (Fed. Cir. Dec. 19, 2008). 

As an interesting point of contrast, since almost 
anything and everything that is a result of nature 
could be viewed as a natural phenomenon, this would 
mean that the statutory proscriptions related to 
patentability would apply to everything. Although 
Justice Frankfurter was noting that an attempt to 
define a law of nature would be futile, in Funk 
Brothers Seed Co., 333 U.S. at 135, his concurring 
opinion stated: 
Everything that happens may be deemed 
“the work of nature,” and any patentable 
composite mixture exemplifies in its prop-
erties the “laws of nature.”  
While  Amici would agree with this statement on its 
face,  Amici would note that, since almost every 
process is impacted by or based upon a law of nature, 
arguments can be drawn for challenging any patent 
based upon those grounds. The end result of this 
reasoning is that nothing, or everything, is pat-
entable, and both results defy logic. 
Amici urge the Court to adopt the two part test 
setting forth the ordinary English definitions set 
forth above. As applied according to that test and 
those definitions, claim 13 of the ’658 patent are not 
drawn to fundamental principles and describe patent-
eligible subject matter. 

A. Personalized Medicine Is A Growing 
Field With A Tremendous Potential To 
Help Patients 
Personalized medicine refers to the tailoring of 
medical treatment to the individualized charac-
teristics of each patient. The technology allows 
physicians to make treatment decisions based on 
molecular markers that signal the presence or risk of 
developing a disease, potential outcome and likeli-
hood that the patient will respond to particular 
therapies. Diagnostic correlations used to identify the 
most effective treatment options for an individual 
patient are critical to personalized medicine.  
The use of diagnostic correlations to select the 
optimal therapy for an individual patient translates 
to improved and more cost-efficient health care for 
all. There are two important issues in selecting a 
treatment: efficacy and risk of side effects. On 
average, a commercial drug works for only 50% of the 
target population.18 Further, every drug and biological 
therapeutic has undesirable side effects, some of 
which can be predicted based on a patient’s drug 
metabolism signature. Published estimates show that 
approximately 5.3% of hospital admissions are 
18 B. Spear, et al., Clinical application of pharma-
cogenomics, Trends Mol. Med. 7(5):201-204 (2001). 

associated with adverse drug reactions (ADRs).19 
Products marketed by personalized medicine com-
panies empower physicians with the ability to treat 
patients with drugs that target the disease while 
minimizing undesirable side effects. Personalized 
medicine products thus spare the patients from 
suffering through ineffective treatment regimes, 
increase the probability of positive outcome and 
decrease the health care costs. 
The Oncotype DX® breast cancer assay, product 
of research conducted by Genomic Health, can predict 
the  likelihood that a patient with early-stage, ER+ 
breast cancer will experience a recurrence of breast 
cancer within 10 years and whether that patient will 
benefit from adding chemotherapy to his/her hor-
monal therapy. The test is based on mRNA levels of 
21 genes, and provides a continuous Recurrence 
Score® (RS) result for each patient that places them 
in a low, intermediate or high risk category. A patient 
with a low RS will not significantly benefit from 
adding chemotherapy, and may be treated with 
hormonal therapy alone. Considering that about 20% 
of patients are in this category, this represents a 
substantial savings (approximately $1930.00 per 
patient) to the health care system and benefit to 
those patients who are spared the unnecessary 
disruption and toxic effects of chemotherapy. On the 
19  C. Kongkaew, et al., Hospital admissions associated with 
adverse drug reactions, Ann Pharmacother 42(7):1017-1025 

other hand, a high RS signals that chemotherapy 
should be added to the patient’s regimen. Used in 
concert with other clinical factors, the Oncotype DX® 
assay can aid physicians and patients in making 
personalized and cost-efficient treatment decisions. 
The selection and validation of the 21 genes, from 
potentially thousands of genes, to use in this test and 
development of RS from the expression levels was the 
culmination of thousands of hours of research by 
highly trained scientists at Genomic Health. The 
selection of 21 genes whose mRNA should be 
monitored was not the discovery of some mere 
principle of nature, rather it was the identification 
that certain arbitrary genes happen to be associated 
with the risk of cancer. HERmark® is a proprietary 
diagnostic of Monogram Biosciences that accurately 
quantifies HER2 total protein expression in patients 
with breast cancer. Preliminary data from three 
cohorts of Herceptin-treated patients with metastatic 
breast cancer who were identified as “HER2 positive” 
by conventional assays suggesting that HERmark® 
can identify patients who are likely to respond to 
trastuzumab with greater precision than currently 
available tests. To date, thousands of hours of re-
search have been involved in developing HERmark®. 
The success of genomics in breast cancer is being 
repeated in other cancers, as well as in other fields. 
For example, about 40% of patients with metastatic 
colon cancer are unlikely to respond to two key 
therapies: cetuximab and panitumumab, because 
these patients have certain KRAS gene mutations. 

Current practice guidelines recommend that only 
patients with the normal KRAS gene sequence be 
treated with chemotherapy, resulting in potential 
savings of approximately $604 million annually if all 
patients are first stratified using the KRAS molecular 
A patient’s genetic profile now allows physicians 
to determine whether a patient will respond to a 
particular therapy, and whether the risk of disease 
for that patient justifies the expense and burden of 
particular therapy. This information has the potential 
to increase patient adherence to treatment regimens, 
decrease costs and failure rates of drug clinical trials 
by focusing on appropriate sub-classifications of 
patients. It is no wonder, then, that the FDA has 
recognized and encouraged the development of per-
sonalized medicine pharmacogenic information, and 
nearly every major pharmaceutical project is in-
corporating information on genetic variation and 
effects on the safety and effectiveness of the 
candidate drug.21 The importance of supporting 
further development of this technology has also been 
recognized by the President’s Council on Science and 
Technology (2008 Report on Priorities for Personalized 
20 National Comprehensive Cancer Network Guidelines in 
Oncology, Colon Cancer, v.2.2009 (available online at http://www. ). 
21  See, e.g., Guidance for Industry on Pharmacogenomic 
Data Submissions (2005); Drug-Diagnostic Co-Development 
Concept Paper (2005); 21 § C.F.R. 201.57. 

Medicine), HHS (Personalized Health Care Initia-
tive,), the Legislature (Genomics and Personalized 
Medicine Act of 2006 (Obama, S. 3822)) and rules and 
comments put forth by many other professional, state 
and federal health care organizations. In her written 
testimony during Senate confirmation hearings, HHS 
Secretary Kathleen Sebelius made the following 
As a result of these contributions to im-
provement in the quality of care, per-
sonalized medicine represents a key strategy 
on healthcare reform. The potential appli-
cation of this new knowledge, especially 
when supported through the use of health 
information technology in the patient care 
setting, presents the opportunity for trans-
formational change.22 
In sum, personalized medicine offers a model for 
efficient and high quality health care.  
22  Katheen Sebelius, written testimony given during Senate 
confirmation hearings, April 2, 2009. 

B.  Because The Machine-Or-Transformation 
Test Endangers Funding For Personal-
ized Medicine Companies, It Will Under-
mine Personalized Medicine Companies, 
Stifle Development And Ultimately Harm 
In his dissent in Lab. Corp. of Am. Holdings
Judge Rader warns us of the consequences of 
endangering funding for personalized medicine. He 
characterized claim 13 of the ’658 patent as patent-
eligible and lamented that denying patent protection 
for such a claim will undermine and discourage 
future research for personalized medicine companies. 
According to Judge Rader: 

. this Court inadvertently advises in-
vestors that they should divert their unpro-
tectable investments away from discovery of 
“scientific relationships” within the body that 
diagnose breast cancer or Lou Gehrig’s 
disease . . .  
Given the long and expensive research, development 
and commercialization cycles and relatively limited 
resources of most personalized medicine companies, 
the patent system is essential to protect and foster 
innovation that, in turn, attracts financial investors. 
Denying valuable patent protection for personalized 
medicine companies will surely advise investors that 
they should divert their unprotectable investments 
away from personalized medicine and, as a result, 
slow the progress of science and harm the interests of 
human patients. 

A strict requirement that a process be tied to a 
particular machine or transform an article could 
exclude much of the technology that drives today’s 
information and knowledge-based economy from 
patent protection, and prospectively hinder innova-
tion in fields of biotechnology, health sciences and 
personalized medicine. The biotechnology industry 
touches upon many essential aspects of the U.S. 
economy, including pharmaceutical therapies, medi-
cal diagnostics, agricultures and industrial processes. 
The biotechnology industry has registered a fast 
growth since the early 1990s. For instance, their 
revenues increased from $8 billion in 1992 to $39.2 
billion in 2003. The job market forecast of biological 
technicians is expected to grow by 28.2 percent be-
tween 2004 and 2014, and that of biological scientists 
is projected to grow by 17.0 percent. In the health 
care sector, the biotechnology industry has more than 
370 therapeutic products currently in clinical trials 
being studied to treat more than 200 diseases. 
Because diagnostic correlating claims would not be 
patentable with a strictly machine-or-transformation 
step, the application of Bilski’s test threatens to 
undermine the development of personalized medicine, 
stem the progress of science and adversely affect the 
health and quality of life of patients. 
Personalized medicine helps patients, and holds 
tremendous potential for improving their lives by its 
ability to more precisely identify potential diseases 
before they arise and select treatment options that 
are specific to the individual. The key to this 

capability is the discovery not of some “scientific 
truth” or “law of nature” or even “natural phenom-
ena.” Rather, it is the discovery, like many medical 
discoveries before now, of certain relationships – 
“correlations.” The discovery of the correlations 
should be patentable subject matter in order to 
encourage and justify investments in the fledgling 
Patents are essential to ensure further research 
and development in personalized medicine and to 
encourage and protect investment. Patent claims 
directed to diagnostic correlations are the key to 
progressing these goals. Patents and the protection 
provided by them foster innovation as way leads on to 
way, one discovery leading on to another, and as other 
personalized medicine companies find other ways to 
help other patients. Perhaps we will be telling this 
story ages and ages hence: that we helped small 
personalized medicine companies improve ourselves. 
And that has made all the difference. 
----------------- ♦ ----------------- 
Requiring, as does the Federal Circuit in Bilski
that all claims recite a “physical” step, such as a 
machine or physical transformation step, jeopardizes 
the future of research in personalized medicine by 
making many biologically-based inventions unpat-
entable under § 101. There is no support for the 
machine-or-transformation test or the idea that only 
physical processes should be patentable, and Amici 

urge the Court to hold that all processes are patent-
eligible.  Amici urge the Court to adopt a rational 
framework for determining patent-eligible subject 
matter that accords with the existing law, one that 
involves determining, as a threshold step, whether a 
fundamental principle (i.e., a law of nature, a 
phenomenon of nature, or an abstract idea) is 
claimed. The test should be simple and elegant and 
the terms law of nature,  natural phenomena and 
abstract idea should be construed in an ordinary 
English sense as universal and having a central role 
in scientific practice and also as being fundamental. 
Once the Court sets forth the test, Amici believe the 
Court will determine that claims to the discovered 
diagnostic corrections are patent-eligible, such as 
claim 13 from the ’658 patent. 
Patents to diagnostic correlations are essential to 
personalized medicine companies to attract the fund-
ing necessary to bring new diagnostics to market. 
Without adequate patent protection, personalized 
medicine companies will suffer, new research will dry 
up and new treatments will not become available to 
Respectfully submitted, 
  Counsel of Record 
801 California Street 
Mountain View, CA 94041 
(650) 988-8500 
  Counsel for Amici Curiae 

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