Caris MPI, Inc.

Patent Trials and Appeals Board

May 28, 2020

IPR2019-00171 (P.T.A.B. May. 28, 2020)

Trials@uspto.gov Paper 57
571-272-7822 Date: May 28, 2020

UNITED STATES PATENT AND TRADEMARK OFFICE

BEFORE THE PATENT TRIAL AND APPEAL BOARD

FOUNDATION MEDICINE, INC.,
Petitioner,
v.
CARIS MPI, INC.,
Patent Owner.

IPR2019-00171
Patent 9,383,365 B2

Before CHRISTOPHER G. PAULRAJ, KRISTI L. R. SAWERT, and
DAVID COTTA, Administrative Patent Judges.
SAWERT, Administrative Patent Judge.

JUDGMENT
Final Written Decision
Determining All Challenged Claims Unpatentable
35 U.S.C. § 318(a)

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I. INTRODUCTION
This is a Final Written Decision in an inter partes review challenging
the patentability of claims 1–14 (“the challenged claims”) of U.S. Patent
No. 9,383,365 B2 (“the ’365 patent,” Ex. 1001). We have jurisdiction under
35 U.S.C. § 6, and enter this Decision pursuant to 35 U.S.C. § 318(a) and
37 C.F.R. § 42.73. For the reasons set forth below, we determine that
Petitioner has shown, by a preponderance of the evidence, that the
challenged claims are unpatentable. See 35 U.S.C. § 316(e) (2012).
A. Procedural History
Foundation Medicine, Inc., (“Petitioner”) filed a Petition for an inter
partes review under 35 U.S.C. § 311. Paper 3 (“Pet.”). Petitioner supported
its Petition with the Declaration of Paul T. Spellman, Ph.D. Ex. 1002. Caris
MPI, Inc. (“Patent Owner”) filed a Preliminary Response. Paper 8. On our
authorization (Paper 9), Petitioner filed a Reply to Patent Owner’s
Preliminary Response (Paper 10) and Patent Owner filed a Sur-Reply to
Petitioner’s Reply (Paper 11).
On May 30, 2019, pursuant to 35 U.S.C. § 314(a), we instituted trial
to determine whether any challenged claim of the ’365 patent is unpatentable
based on the grounds raised in the Petition:
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Claims Challenged 35 U.S.C. § Reference(s)/Basis
1–14 103(a)1 Lu,2 Illumina3
2, 3 103(a) Lu, Illumina, Muraca4
7, 11 103(a) Lu, Illumina, McDoniels-Silvers5
Paper 13, 8, 31–32 (“Institution Decision” or “Inst. Dec.”).
Patent Owner filed a Response. Paper 33 (“PO Resp.”). Patent
Owner supported its Response with the Declaration of Joyce
O’Shaughnessy, M.D. Ex. 2021. Petitioner filed a Reply to Patent Owner’s
Response. Paper 43 (“Pet. Reply”). Petitioner supported its Reply with a
Reply Declaration of Dr. Spellman. Ex. 1120. Patent Owner filed a Sur-
Reply. Paper 51 (“PO Sur-Reply”).

1 The Leahy-Smith America Invents Act (“AIA”), Pub. L. No. 112-29,
125 Stat. 284, 287–88 (2011), amended 35 U.S.C. § 103, effective March 16,
2013. Because the challenged claims have an effective filing date before
this date, the pre-AIA version of § 103 applies.

2 Mou-Ying Fu Lu and Rong Yu, WO 03/017038 A2 (Feb. 27, 2003)
(“Lu,” Ex. 1004).
3 Illumina® Gene Expression Profiling, Technical Bulletin, RNA
Profiling with the DASL® Assay (2005) (“Illumina,” Ex. 1005).
4 Patrick J. Muraca, U.S. Patent Application Publication
No. 2002/0150966 A1 (Oct. 17, 2002) (“Muraca,” Ex. 1006).
5 Amy L. McDoniels-Silvers et al., Differential Expression of
Critical Cellular Genes in Human Lung Adenocarcinomas and
Squamous Cell Carcinomas in Comparison to Normal Lung
Tissues, 4(2) NEOPLASIA 141–50 (2002) (“McDoniels-Silvers,”
Ex. 1007).
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An oral hearing was held on March 6, 2020. A transcript of the
hearing is included in the record. Paper 55 (“Tr.”).
B. Real Parties in Interest
Petitioner identifies Foundation Medicine, Inc. and Roche Holdings,
Inc., Roche Finance Ltd., and Roche Holding Ltd. as real parties-in-interest.
Pet. 2. Patent Owner identifies Caris MPI, Inc., Caris Molecular
Diagnostics, and Caris Life Sciences, Ltd. as real parties-in-interest.
Paper 4, 2.
C. Related Matters
The ’365 patent is the subject of a co-pending litigation in the United
States District Court for the District of Massachusetts captioned Civil Action
No: 1:17-cv-12194-MLW. Pet. 2; Paper 4, 2. According to Petitioner, that
case remains pending, but is currently stayed. Paper 23, 1.
The following Board proceedings also involve the same parties:
IPR2019-00164 (U.S. Patent No. 8,880,350 B2), IPR2019-00165 (U.S.
Patent No. 9,092,392 B2), IPR2019-00166 (U.S. Patent No. 9,292,660 B2),
IPR2019-00170 (U.S. Patent No. 9,372,193 B2), and IPR2019-00203 (U.S.
Patent No. 9,292,660 B2). Final Written Decisions in IPR2019-00166 and
IPR2019-00203 issued on May 13, 2020. See IPR2019-00166 (Paper 53);
IPR2019-00203 (Paper 53). Final Written Decisions in IPR2019-00164 and
IPR2019-00170 issued on this day. See IPR2019-00164 (Paper 55);
IPR2019-00170 (Paper 56). Institution of an inter partes review in
IPR2019-00165 was denied. IPR2019-00165, Paper 7.
D. Summary of the ’365 Patent
The ’365 patent, titled “System and Method for Determining
Individualized Medical Intervention for a Disease State,” issued on July 5,
2016. Ex. 1001, codes (54), (45). The ’365 patent relates to a “system and
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method for determining individualized medical intervention for a particular
disease state,” such as cancer, that “includes the molecular profiling of a
biological sample from the patient.” Id. at Abstract.
According to the ’365 patent, “[a]lthough the molecular mechanisms
behind various disease states have been the subject of studies for years, the
specific application of a diseased individual’s molecular profile in
determining treatment regimens and therapies for that individual has been
disease specific and not widely pursued.” Id. at 1:45–49. The ’365 patent
further states that “[s]ome treatment regimens have been determined using
molecular profiling in combination with clinical characterization of a patient
such as observations made by a physician . . . , laboratory test results, x-rays,
biopsy results, statements made by the patient, and any other medical
information typically relied upon by a physician to make a diagnosis in a
specific disease.” Id. at 1:50–58 (emphasis added). The ’365 patent states
that this combination approach “presents a risk that an effective treatment
regimen may be overlooked for a particular individual” because some
treatment regimens traditionally administered for one particular disease state
also may be effective in treating a different disease state. Id. at 1:58–65.
Thus, the ’365 patent states, “there is a need for a system and method
for determining an individualized medical intervention” for a patient that can
identify “additional targets” or “molecular mechanisms, genes, gene
expressed proteins and/or combinations of such.” Id. at 2:20–25, 30–31.
The ’365 patent states that this approach would provide patients “with a
viable therapeutic alternative to those treatment regimens which currently
exist.” Id. at 2:25–29. Figure 2 of the ’365 patent, reproduced below,
provides an overview of “an exemplary embodiment of a method for
determining individualized medical intervention for a particular disease state
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that utilizes molecular profiling of a patient’s biological specimen that is non
disease specific.” Id. at 5:4–7, 13:15–19.

Figure 2 provides an overview of a method for determining an
individualized medical intervention that utilizes a patient’s
molecular profile. Id.
In step 52 of Figure 2, at least one test is performed for at least one
molecular target (e.g., one or more genes, proteins, and/or molecular
mechanisms) from a patient’s biological sample. Id. at 13:19–23. Tests that
may be performed include immunohistochemistry (IHC) analysis 54,
microarray analysis 56, and/or any other known molecular tests 58. Id. at
13:35–38. The ’365 patent states that IHC analysis may be performed for
such proteins as c-kit, EGFR, MLH1, and PDGFR. Id. at 2:67–3:4.
Microarray analysis may be performed for such genes as ESR1, PDGFRA,
PTEN, and TOP1. Id. at 3:5–23.
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In step 60, “a determination is made as to whether one or more of the
targets that were tested for in step 52 exhibit a change in expression
compared to a normal reference for that particular target.” Id. at 13:47–50.
A change in expression may be observed via differential staining 64, the
amount of overexpression or underexpression 66, and/or “by an absence of
one or more genes, gene expressed proteins, molecular mechanisms, or other
molecular findings.” Id. at 13:50–14:3.
Next, “at least one non-disease specific agent is identified that
interacts with each target having a changed expression in step 70.” Id. at
14:4–7. The ’365 patent states that a “non-disease specific agent” “is a
therapeutic drug or compound not previously associated with treating the
patients diagnosed disease that is capable of interacting with the target from
the patient’s biological sample that has exhibited a change in expression.”
Id. at 14:8–12.
Finally, in step 80, “a patient profile report may be provided which
includes the patient’s test results for various targets and any proposed
therapies based on those results.” Id. at 14:28–30. Figures 3A through 3D
of the ’365 patent illustrate an “exemplary patient profile report in
accordance with step 80” of Figure 2. Id. at 5:8–9. Figure 3A is reproduced
below.
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Figure 3A illustrates an exemplary patient profile report 100. Id.
The report 100 lists the molecular targets profiled 102, the targets
tested that exhibited significant changes in expression 104, and the proposed
therapeutic agents for interacting with the targets 106. Id. at 14:31–35.
The ’365 patent discloses a computerized system for generating the
report, which includes, among other things, an application program stored in
a memory that is accessible by a processor, internal databases, and external
databases. Id. at 12:47–55. The internal databases can include information
about the patient biological sample, patient test results from molecular
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profiling, clinical data, and study protocols. Id. at 12:50–13:12. The
external databases can include drug libraries, gene libraries, disease libraries,
and public databases such as GenBank. Id. at 13:8–12. The ’365 patent
states that the processor comprises instructions for assessing a patient’s
molecular profile, determining whether at least one molecular target exhibits
a change in expression “compared to a normal reference,” and accessing a
drug therapy database to identify drug therapies. Id. at 4:4–24. The ’365
patent states that a drug therapy may be identified “from an automated
review of an extensive literature base and/or an automated review of data
generated from clinical trials.” Id. at 4:45–49.
E. Illustrative Claim
Of the challenged claims, claim 1 is independent and illustrative of the
claimed subject matter. Claim 1 recites:
1. A system for generating a report identifying at least one
therapeutic agent for an individual with a cancer comprising:

a. at least one device configured to assay a plurality of molecular
targets in a biological sample to determine molecular
profile test values for the plurality of molecular targets,
wherein the plurality of molecular targets comprises
EGFR, KIT, TOP1, MLH1, PTEN, PDGFRA and
ER[B]B26; and
b. at least one computer database comprising:
i. a reference value for each of the plurality of molecular
targets; and
ii. a listing of available therapeutic agents for each of the
plurality of molecular targets;

6 As noted in our Institution Decision, we understand that the
recitation of “ERRB2” in claim 1 of the ’365 patent is an obvious
typographical error. Inst. Dec. 6 n.1; see also Pet. 24 n.4. Therefore, we
refer to “ERBB2,” rather than “ERRB2.”
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c. a computer-readable program code comprising instructions to
input the molecular profile test values and to compare
each of the molecular profile test values with a
corresponding reference value from the at least one
computer database in (b)(i);

d. a computer-readable program code comprising instructions to
access the at least one computer database and to identify
at least one therapeutic agent from the listing of available
therapeutic agents for the plurality of molecular targets
wherein the comparison to the reference values in (c)
indicates a likely benefit of the at least one therapeutic
agent; and

e. a computer-readable program code comprising instructions to
generate a report that comprises a listing of the molecular
targets for which the comparison to the reference value
indicated a likely benefit of the at least one therapeutic
agent in (d) and the at least one therapeutic agent
identified in (d).
Ex. 1001, 17:5–35.
II. ANALYSIS
We have reviewed the parties’ respective briefs as well as the relevant
evidence discussed in those papers. For the reasons discussed in detail
below, we determine that Petitioner has shown by a preponderance of the
evidence that claims 1–14 of the ’365 patent are unpatentable under 35
U.S.C. § 103 as having been obvious.
A. Principles of Law
To prevail in its challenges to the patentability of all claims of the
’365 patent, Petitioner must demonstrate by a preponderance of the evidence
that the claims are unpatentable. 35 U.S.C. § 316(e) (2012); 37 C.F.R.
§ 42.1(d) (2018). “In an [inter partes review], the petitioner has the burden
from the onset to show with particularity why the patent it challenges is
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unpatentable.” Harmonic Inc. v. Avid. Tech., Inc., 815 F.3d 1356, 1363
(Fed. Cir. 2016); see also 35 U.S.C. § 312(a)(3) (requiring inter partes
review petitions to identify “with particularity . . . the evidence that supports
the grounds for the challenge to each claim”). That burden of persuasion
never shifts to Patent Owner. Dynamic Drinkware, LLC v. Nat’l Graphics,
Inc., 800 F.3d 1375, 1378 (Fed. Cir. 2015); see also In re Magnum Oil Tools
Int’l, Ltd., 829 F.3d 1364, 1375–78 (Fed. Cir. 2016) (discussing the burden
of proof in inter partes review).
A claim is unpatentable for obviousness if, to one of ordinary skill in
the pertinent art, “the differences between the subject matter sought to be
patented and the prior art are such that the subject matter as a whole would
have been obvious at the time the invention was made.” 35 U.S.C. § 103(a)
(2006); see also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406 (2007).
The question of obviousness is resolved on the basis of underlying factual
determinations including the scope and content of the prior art, any
differences between the claimed subject matter and the prior art, the level of
ordinary skill in the art, and objective evidence of nonobviousness. Graham
v. John Deere Co., 383 U.S. 1, 17–18 (1966). A petitioner cannot satisfy its
burden of proving obviousness by employing “mere conclusory statements.”
Magnum Oil, 829 F.3d at 1380. Moreover, a decision on the ground of
obviousness must include “articulated reasoning with some rational
underpinning to support the legal conclusion of obviousness.” KSR, 550
U.S. at 418 (citing In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006)).
We analyze Petitioner’s asserted grounds of unpatentability in
accordance with the above-stated principles.
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B. Level of Ordinary Skill in the Art
We consider the asserted grounds of unpatentability in view of the
understanding of a person of ordinary skill in the art, and thus begin with the
level of ordinary skill in the art. The level of ordinary skill in the art is “a
prism or lens through which . . . the Board views the prior art and claimed
invention” to prevent hindsight bias. Okajima v. Bourdeau, 261 F.3d 1350,
1355 (Fed. Cir. 2001).
The parties dispute the level of ordinary skill in the art. Relying on
the declaration testimony of its declarant, Dr. Spellman, Petitioner contends
that as of May 18, 2006—the earliest filing date in the priority chain for the
’365 patent—a person of ordinary skill in the art “would have had a Ph.D. in
genetics, molecular biology, bioinformatics, or a related field, and at least
five years of research experience in an academic or industry setting,
including at least two to three years of research experience in the field of
cancer genomics.” Pet. 16 (citing Ex. 1002 ¶ 32). In our Institution
Decision, we preliminarily adopted this level of ordinary skill, which Patent
Owner did not dispute in its Preliminary Response. Inst. Dec. 8–9. We also
determined that the prior art itself was sufficient to demonstrate the level of
ordinary skill in the art at the time of the invention. Id.
In response, Patent Owner disputes the type of experience Petitioner
proposes for the level of ordinary skill in the art. See PO Resp. 4–8; PO Sur-
Reply 4–8. Relying on the declaration testimony of its declarant,
Dr. O’Shaughnessy, Patent Owner argues that the ordinarily skilled artisan
“is an oncologist having a medical degree, at least 10 years of experience
treating cancer patients at a medical research facility or hospital, and
experience with clinical trials involving anti-cancer therapeutic agents.” PO
Resp. 4 (citing Ex. 2021 ¶ 14). Patent Owner argues that the ’365 patent
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“details treatment selection and the molecular profiling of cancer patients for
treatment recommendations.” Id. at 4–5 (citing Ex. 1001, 12:50–14:64).
Thus, Patent Owner argues, the ordinarily skilled artisan is “an oncologist
because oncologists are the people who treat cancer patients and therefore
need to understand which anti-cancer therapies are more or less likely to be
of therapeutic benefit to their patients.” Id. at 5 (citing Ex. 2021 ¶ 14).
Patent Owner argues that Petitioner’s definition of an ordinarily
skilled artisan is incorrect because Ph.D. researchers “do not treat or select
therapy options for cancer patients, and their research findings are not
allowed to contribute to the medical record or form the basis for clinical
decision-making.” Id. at 5 (citing Ex. 2068, 126:5–127:8). Instead, a
researcher “studies the molecular bases of various cancers to develop new
molecular assays to inform, for example, the development of new drugs.”
Id. at 5–6 (citing Ex. 1002 ¶¶ 6, 14). But, Patent Owner argues, “[t]he
development of new molecular assays is not the field of the claimed
invention,” and therefore, “a researcher focused on developing molecular
assays cannot be a [person of ordinary skill in the art].” Id. at 6.
Patent Owner also argues that the nature of the problem to be solved
by the claimed invention supports its definition of an ordinarily skilled
artisan. PO Sur-Reply 4–8. Specifically, Patent Owner argues that the
prior-art problem “was how to identify treatment options for cancer
patients,” and “[w]hile the solution entailed the use of molecular testing
methods,” those methods are merely tools used to implement “the idea of
using data from assays to identify treatment options independent of cancer
lineage.” Id. at 4–5 (citing Ex. 1118, 99:6–22, 100:2–101:2, 101:13–20).
Based on our consideration of the full record, we maintain our
determination that a person with a Ph.D. in genetics, molecular biology,
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bioinformatics, or a related field, and at least five years of research
experience in an academic or industry setting, including at least two to three
years of research experience in the field of cancer genomics, would satisfy
the definition of an ordinarily skilled artisan in this proceeding. We further
find that, although the ordinarily skilled artisan may have a medical degree
instead of, or in addition to, a Ph.D., that artisan need not be a practicing
oncologist with experience treating cancer patients.
In determining the level of ordinary skill, various factors may be
considered, including “(1) the educational level of the inventor; (2) type of
problems encountered in the art; (3) prior art solutions to those problems;
(4) rapidity with which innovations are made; (5) sophistication of the
technology; and (6) educational level of active workers in the field.” Daiichi
Sankyo Co. v. Apotex, Inc., 501 F.3d 1254, 1256 (Fed. Cir. 2007). These
factors are “merely a guide,” and the weight or significance ascribed to each
depends on the particular case. Id. In this particular case, we find that the
factors, overall, support Petitioner’s definition of an ordinarily skilled
artisan.
The “problem” identified in the ’365 patent is selecting treatment
based on “clinical based criteria,” i.e., “the determination that the patient has
been diagnosed with a particular disease” via “classical diagnostic assays.”
Ex. 1001, 1:39–44. The ’365 patent purports to solve that problem by
utilizing “molecular profiling,” i.e., by generating a “diseased individual’s
molecular profile” and using that profile, instead of “clinical
characterizations (such as the diagnosis of a particular type of cancer)[,] to
determine a treatment regimen or therapy.” Id. at 1:50–58. The ’365 patent
further criticizes using “molecular profiling in combination with clinical
characterization of a patient such as observations made by a physician,”
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because the use of “medical information typically relied upon by a physician
to make a diagnosis in a specific disease” “presents a risk that an effective
treatment regimen may be overlooked for a particular individual.” Id. at
1:50–65 (emphasis added). According to the ’365 patent, molecular
profiling can identify “additional targets” or “molecular mechanisms, genes,
gene expressed proteins and/or combinations of such,” to provide patients
“with a viable therapeutic alternative to those treatment regimens which
currently exist.” Id. at 2:20–29.
In addition, claim 1 is directed to a computerized system for
generating a report identifying at least one therapeutic agent for an
individual with a cancer comprising “at least one device configured to assay
a plurality of molecular targets.” Id. at 17:5–7. The detailed description of
the ’365 patent focuses on “various system components,” “various
databases” (including molecular profiling databases), and communications
and displays for generating the report for an end user. See id. at 5:40–13:12.
The claim language also recites “at least one device configured to assay a
plurality of molecular targets,” “at least one computer database,” and
“computer-readable program code” comprising instructions to perform
various functions of the computerized system. Id. at 17:7–35.
We are not persuaded by Patent Owner’s arguments that an ordinarily
skilled artisan would necessarily be an oncologist who treats patients. As
noted above, the ’365 patent teaches away from treatment decisions made
from “classical diagnostic assays” and “clinical characterization of a patient
such as observations made by a physician.” Ex. 1001, 1:39–65. And,
although Patent Owner argues that the only “[o]ncologists are the persons
qualified to make recommendations for treatments,” PO Sur-Reply 5, the
’365 patent teaches instead the “the step of identifying a drug therapy”
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comes “from an automated review of an extensive literature base and/or an
automated review of data generated from clinical trial,” Ex. 1001, 4:45–49
(emphases added). We are persuaded by Dr. Spellman’s testimony, as
supported by record evidence, that it was “researchers in [his] field” that
“were working to associate molecular profiles to potential cancer therapies.”
Ex. 1120 ¶ 11; see also Ex. 1036, 2236 (prior-art database disclosing “120
targets covering 72 disease conditions together with 120 sets of drugs
directed at each of these targets”), Ex. 1037, 412 (prior-art “therapeutic
target database”). In this regard, although the claimed system could be used
by an oncologist as an end-user to help guide treatment decisions,
development of the claimed system requires knowledge of “molecular
mechanisms, genes, gene expressed proteins and/or combinations of such,”
Ex. 1001, 2:20–23, that was typically performed by Ph.D. researchers, see
Ex. 1120 ¶ 11. Thus, we find that the experience and education level of an
oncologist would be less relevant for assessing patentability issues for the
’365 patent than a Ph.D. researcher with several years’ experience in the
field of cancer genomics.
Moreover, the claimed system also requires knowledge of computer
systems and databases. See id. at 5:40–13:10. The type of experience Patent
Owner argues is necessary in this case—i.e., experience in treating
patients—bears little relevance to computerized systems and databases. See,
e.g., Ex. 1119, 398:13–20 (Dr. O’Shaughnessy’s testimony that she is not
“qualified to make comments about” prior-art reference Lu’s “computerized
decision support system and databases” in the context of a question of
“cancer lineage independence”).
Finally, with respect to the educational level of the inventors and the
ordinarily skilled artisan, we note that the educational levels and years of
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experience for both parties’ proposed definitions (a Ph.D. and a M.D.) are
high. Generally, “[a] less sophisticated level of skill generally favors a
determination of nonobviousness, and thus the patentee, while a higher level
of skill favors the reverse.” Innovention Toys, LLC v. MGA Entm’t, Inc.,
637 F.3d 1314, 1323 (Fed. Cir. 2011). Thus, although we agree with and
have adopted Petitioner’s definition for an ordinarily skilled artisan in this
proceeding, our analysis and conclusions herein would not change even
under Patent Owner’s definition. We have considered the qualifications of
Dr. Spellman and Dr. O’Shaughnessy, and find that both are qualified to
provide opinions about the ’365 patent from the perspective of an ordinarily
skilled artisan. See Ex. 1002, Exhibit A (Dr. Spellman’s curriculum vitae);
Ex. 2021, Exhibit A (Dr. O’Shaughnessy’s curriculum vitae).
C. Claim Construction
Having defined the ordinarily skilled artisan, we now turn to claim
construction. For petitions filed before November 13, 20187—as here—the
Board interprets claims in an unexpired patent using the “broadest
reasonable construction in light of the specification of the patent.” 37 C.F.R.
§ 42.100(b) (2018); Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131,
2144–46 (2016). Under that standard, we presume that a claim term carries
its “ordinary and customary meaning,” which “is the meaning that the term
would have to a person of ordinary skill in the art in question” at the time of
the invention. In re Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir.

7 See Changes to the Claim Construction Standard for Interpreting
Claims in Trial Proceedings Before the Patent Trial and Appeal Board, 83
Fed. Reg. 51,340 (Oct. 11, 2018) (amending 37 C.F.R. § 42.100(b) effective
November 13, 2018 to require a federal district court claim construction
approach) (now codified at 37 C.F.R. § 42.100(b) (2019)).
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2007). We need not explicitly interpret every claim term for which the
parties propose a construction. See 35 U.S.C. § 314(a) (2012); Vivid Techs.,
Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999) (“[O]nly
those terms need be construed that are in controversy, and only to the extent
necessary to resolve the controversy.”); see also Nidec Motor Corp. v.
Zhongshan Broad Ocean Motor Co., 868 F.3d 1013, 1017 (Fed. Cir. 2017)
(applying Vivid Techs. in the context of an inter partes review).
At the close of trial, the only claim-construction dispute remaining in
this proceeding is whether the claims require, as Patent Owner argues, a
system that is “cancer-lineage independent.” PO Resp. 24–25. Briefly,
Patent Owner argues that a “cancer-lineage independent” system is one that
“identif[ies] treatment options for a cancer patient independent of cancer
type, based on groups of molecular targets not traditionally or
conventionally associated with the patient’s specific cancer type.” Id. at 1.
Patent Owner argues that the claims do not encompass a “cancer-lineage
dependent” system, which, according to Patent Owner, “compares the
genetic profile of a patient’s tumor with various genes and mutations
associated with the same type of cancer, and then selects drugs from a
database of drugs known to treat that particular type of cancer.” Id. at 2.
Petitioner contends that “Patent Owner’s construction reads in ‘cancer-
lineage independence,’” and that “the claims are not limited to a system for
identifying a cancer lineage-independent therapeutic agent.” Reply 6.
1. Overview of Patent Owner’s Arguments
Patent Owner argues that cancer-lineage independence is required by
the preamble as well as sections (a) and (b) of claim 1. PO Resp. 24–35; see
also PO Sur-Reply 8–20. As to the preamble, Patent Owner argues that an
ordinarily skilled artisan would have understood “a cancer” to mean “any
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type of cancer.” PO Resp. 27–28. As to section (a), Patent Owner argues
that an ordinarily skilled artisan would have understood that the group of
molecular targets identified in that section (i.e., EGFR, KIT, TOP1, MLH1,
PTEN, PDGFRA, and ERBB2) “is a pan-cancer or lineage-independent
group of molecular targets.” Id. at 28. Turning to section (b), Patent Owner
argues that section (b)(i) requires a database to store a reference value for
“each of the plurality of molecular targets” listed in section (a), while section
(b)(ii) requires the database to store “a listing of available therapeutic
agents” for each of the plurality of molecular targets. Id. at 29. Patent
Owner argues that “[t]he ‘available therapeutic agents’ are not limited to
agents for the patient’s specific type of cancer, so the database of section (b)
is therefore also cancer lineage independent.” Id.
Patent Owner also argues that section (c) and (d) of claim 1 reaffirm
the cancer lineage-independence requirements of sections (a) and (b). Id. at
29–31. Specifically, Patent Owner argues that section (c)’s “claimed
comparison” of the patient’s molecular profile test values with reference
values in section (b)(i) “is not based on the lineage of the patient’s cancer.”
Id. at 30. And, as to section (d), Patent Owner argues that “[i]t is undisputed
that in 2006, at least one therapeutic agent with potential efficacy was
associated with each of the molecular targets listed in section (a).” Id. at 31.
“As a result,” Patent Owner argues, “sections (c) and (d) must compare each
of the listed molecular targets against reference values and be capable of
identifying all available therapeutic agents for those molecular targets
independent of cancer lineage.” Id. at 31.
2. Overview of Petitioner’s Arguments
Petitioner disputes Patent Owner’s position. See Reply 6–13. In
particular, Petitioner contends that Patent Owner’s reading of claim 1
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“imports a narrowing limitation from the specification without any basis in
the claims or intrinsic evidence.” Id. at 6. Petitioner contends that the claim
language does not require lineage independence, and that Patent Owner has
identified “no explicit lineage-independence term in the claims.” Id. at 7.
As to sections (a) and (b) of claim 1, Petitioner contends that “those
limitations are unambiguous and do not justify Patent Owner’s
construction.” Id. at 7. Petitioner also contends that Patent Owner’s
construction conflicts with the prosecution history of the ’365 patent family,
id. at 8–9, and that “importing a lineage-independence limitation would
render the claims indefinite,” id. at 10–12.
3. Analysis
We begin with the words of claim 1 itself. See Amgen Inc. v. Hoechst
Marion Roussel, Inc., 457 F.3d 1293, 1301 (Fed. Cir. 2006) (“[C]laim
construction must begin with the words of the claims themselves.”). As
explained above, the parties dispute whether claim 1 requires that the system
is a “cancer-lineage independent system”—that is, does not encompass the
allegedly “cancer-lineage dependent” systems of the prior art. For the
reasons provided below, we determine that the broadest reasonable
interpretation of claim 1 does not require the system to be “cancer-lineage
independent.”
We see nothing explicit in the plain language of claim 1 that requires
the claimed system to be a “cancer-lineage independent” system. See
Ex. 1001, 17:5–35. The written description of the ’365 patent uses phrases
such as “independent of disease lineage diagnosis,” id. at 2:34–35, 13:20–
21, and “not single disease restricted,” id. at 2:47–49, 13:21–22, to convey
the concept of identifying a therapeutic agent independently of cancer
lineage. But claim 1 fails to explicitly recite such language relating to
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cancer lineage. Instead, the plain words of the claim are broadly addressed
to a system that determines the molecular profile for an individual with a
cancer and generates a report identifying at least one therapeutic agent8
based on that individual’s molecular profile. See Ex. 1001, 17:5–35.
Moreover, we note that the plain words of the claim are not directed to
a method of treating a patient with a cancer-lineage independent approach,
as Patent Owner implies. See PO Resp. 14 (characterizing the claimed
subject matter as setting forth “a paradigm changing approach to treating
cancer”). The plain words of the claim are instead directed to a system that
generates a report identifying at least one therapeutic agent. See Ex. 1001,
17:5–6 (preamble reciting a “system for generating a report identifying at
least one therapeutic agent”); id. at 17:30–31 (section (e) reciting
“comprising instructions to generate a report”). As noted above, Patent
Owner distinguishes a “cancer-lineage independent” system from a “cancer-
lineage dependent” system, in part, by emphasizing that a “cancer-lineage
dependent” system “selects drugs from a database of drugs known to treat
that particular type of cancer,” i.e., an on-label therapeutic agent. PO Resp.
2. But claim 1 does not require that the “at least one therapeutic agent”
listed in the report be a “non-disease specific agent” (i.e., an off-label
therapeutic agent) as expressly defined in the ’365 patent. See Ex. 1001,
14:8–12 (defining “non-disease specific agent” as “a therapeutic drug or
compound not previously associated with treating the patient’s diagnosed

8 The parties sometimes refer to therapeutic agents as either “on-
label,” meaning that the therapeutic agent has been indicated for a patient’s
particular type of cancer, or “off-label,” meaning that the therapeutic agent
has not been indicated for a patient’s particular type of cancer. See, e.g., PO
Sur-Reply 2; Reply 8. For clarity, we do the same throughout this Decision.
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disease that is capable of interacting with the target from the patient’s
biological sample that has exhibited a change in expression” (emphasis
added)); see also PO Sur-Reply 2 (defining “off-label” as “the identified
therapy will not be indicated for the patient’s cancer”). Moreover, the report
itself is agnostic as to whether a physician reading it will apply the concept
of cancer-lineage independence to selecting treatments for cancer patients.
See Ex. 1001, Fig. 3D (“Decisions regarding care and treatment should not
be based on a single test such as this test. Rather, decisions on care and
treatment should be based on the independent medical judgment of the
treating physician taking into consideration all available information . . . .”).
Turning to other intrinsic evidence, we are persuaded by Petitioner’s
contentions that the prosecution histories of related applications undermine
Patent Owner’s argument that claim 1 requires a cancer-lineage independent
system. Reply 8–9. The ’365 patent claims priority through another
application to application No. 11/750,721 (“the ’721 application,” now U.S.
Patent 8,700,335), and provisional application No. 60/747,645 (“the
provisional application”). Ex. 1001, codes (63), (60). Claim 12 of the
provisional application expressly limited the claimed method to “identifying
a drug therapy . . . that is not single disease restricted.” Ex. 1139, 26
(emphasis added). Original claim 1 of the ’721 application (a parent
application of the ’365 patent) also expressly recited “not single disease
restricted.” Ex. 1141, 635. This language was amended in a preliminary
amendment to “has not been previously associated with treating the
diagnosed disease.” Id. at 531; see also id. at 408 (amending claim 1 to
recite “wherein the drug therapy has not previously been used to treat the
diagnosed disease”). Because the written description of the ’365 patent
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equates disease-lineage independence with “not single disease restricted,”9
we find that these claims were explicitly limited to the concept of cancer-
lineage independence. See Ex. 1001, 13:20–22 (reciting “independent of
disease lineage diagnosis (i.e. not single disease restricted)”); see also
Ex. 1141, 627 (¶ 53) (accord); Edwards Lifesciences LLC v. Cook Inc., 582
F.3d 1322, 1334 (Fed. Cir. 2009) (stating that “i.e.” “signals an intent to
define the word to which it refers”).
Over the course of prosecution of the related applications, however,
claims making clear that the invention requires cancer-lineage independence
were amended to remove that language, and/or canceled. See Ex. 1141, 531
(amending claim 1), 239 (canceling claim 1). For example, claim 21—the
claim ultimately issued as claim 1 of the U.S. Patent 8,700,335—originally
recited “has not previously been associated with treating the diagnosed
disease.” Id. at 536. But, before allowance, the claim was amended to
remove this language and instead recite limitations similar to those found in
the ’365 patent. See id. at 81 (showing final amendments to claim 21).

9 Patent Owner also appears to make a distinction between a “non-
disease specific” system and a “non-disease specific” therapeutic agent, and
implies that the prosecution histories are irrelevant because the former is a
requirement of claim 1 but the latter is not. PO Resp. 32 n.90; PO Sur-Reply
18–19. To the extent Patent Owner’s argument is properly presented, we
reject it because Patent Owner itself loosely uses the phrase “cancer-lineage
independent” throughout its arguments to modify both the claimed system
and the therapeutic agents. Compare, e.g., PO Resp. 2 (referring to a
“cancer lineage-independent approach”), with id. at 3 (stating that “the
treatment options provided to the oncologist are cancer lineage-
independent”). The ’365 patent also expressly uses the phrase “that is
independent of disease lineage diagnosis” to modify “molecular profiling.”
Ex. 1001, 13:20–21.
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We find that this prosecution history provides strong evidence that
Patent Owner knew how to describe and claim the concept of cancer-lineage
independence, but chose not to—both for the method claims of the ’721
application and for the system claims here. See Microsoft Corp. v. Multi–
Tech Sys., Inc., 357 F.3d 1340, 1350 (Fed. Cir. 2004) (“Any statement of the
patentee in the prosecution of a related application as to the scope of the
invention would be relevant to claim construction[.]”); Biovail Corp. Intern.
v. Andrx Pharmaceuticals, Inc., 239 F.3d 1297 (Fed. Cir. 2001) (stating that
“[c]laim language . . . must be read consistently with the totality of the
patent’s applicable prosecution history,” including prosecution histories of
earlier applications). Indeed, Patent Owner could have expressly recited any
of above-described terms (“not single disease restricted,” “has not been
previously associated with treating the diagnosed disease,” or “wherein the
drug therapy has not previously been used to treat the diagnosed disease”) if
it intended claim 1 to be limited to a cancer-lineage independent paradigm.
But Patent Owner chose not to use such language to describe the claimed
invention. For these reasons, we are not persuaded by Patent Owner’s
argument that “[t]he file histories of the ’365 patent and related patents
reinforce [its] interpretation of the claims.” PO Sur-Reply 15.10

10 Patent Owner also argues that an Interview Summary from the
prosecution history of related application 11/750,721 “shows that the
applicants and the Examiner understood that the invention related to ‘lineage
of cancer.’” PO Sur-Reply 13 (citing Ex. 1141, 113). Even so, the
Interview Summary does not provide persuasive evidence that the claims
here require “cancer-lineage independence.” The Interview Summary states
that the applicant and the Examiner “[d]iscussed applicant proposed
amendment to the claims.” Ex. 1141, 113. The Interview Summary also
states that, “It was further discussed the recitation of ‘lineage of cancer’
however no agreement was met.” Id. Following the interview, Patent
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We also disagree with Patent Owner’s argument that, even though
explicit limitations relating to cancer lineage were removed during
prosecution, other language in claim 1 requires a “cancer-lineage
independent” system. See PO Resp. 27–31 (arguing that the concept of
cancer-lineage independence is claimed through the recitation of “a cancer”
in the preamble of claim 1, a “plurality of molecular targets” in section (a), a
“listing of available therapeutic agents” therefor in section (b), as well as
sections (c) and (d)); see also PO Sur-Reply 9 (arguing that an ordinarily
skilled artisan “reading claim 1 would understand that the preamble and
sections (a), (b), (c), and (d) of claim 1 collectively define a system that
identifies therapies for a cancer patient independent of cancer lineage”).
First, as discussed above, reading “cancer-lineage independence” into
the claim would be contrary to the applicant’s intent to remove this concept
from the claims during prosecution of a parent application of the ’365 patent.
See Laryngeal Mask Co. v. Ambu, 618 F.3d 1367, 1373 (Fed. Cir. 2010)
(stating that “it would be improper to read” into a claim a limitation removed
by amendment, regardless of why eliminated (citing Kistler Instrumente AG
v. United States, 628 F.2d 1303, 1308 (Ct. Cl. 1980) (“[D]efendant's
insist[e]nce upon this court’s reading back into the claims limitations which
were originally there and were removed during prosecution of the
application through the Patent Office cannot be permitted.”))).

Owner did not amend the claims to refer to “lineage of cancer” (whether
independent or dependent), or use other words relating to cancer-lineage
independence. See id. at 81. Thus, if anything, this evidence suggests that
applicant did not intend to limit the claims to a cancer-lineage independent
system.
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Second, we find Patent Owner’s attempt to inject the concept of
cancer lineage-independence into claim 1 confusing and unhelpful to
construing the actual words of that claim. Specifically, Patent Owner’s
claim-construction path requires us to start with words in the preamble (“a
disease”), then move on to the listing of molecular targets in section (a)
(“EGFR, KIT, TOP1, MLH1, PTEN, PDGFRA, and ERBB2”), then add to
that “a listing of available therapeutic agents” in section (b), and finish with
the “comparison” terms in sections (c) and (d) to come to the result that
claim 1 requires “cancer-lineage independence.” See PO Resp. 27–31.
Although we understand that the claim language must be considered “as a
whole,” Pozen Inc. v. Par Pharm., Inc., 696 F.3d 1151, 1161 (Fed. Cir.
2012), Patent Owner’s arguments fail to add clarity to the plain words of the
claim, see Dayco Prod., Inc. v. Total Containment, Inc., 258 F.3d 1317,
1324 (Fed. Cir. 2001) (“If an argument offered in support of a particular
claim construction is so convoluted and artificial that it would not be
apparent to a skilled artisan reading the patent and the prosecution history,
the argument is simply unhelpful to the performance of our [claim-
construction] task.”). For these reasons, we see no reason to depart from the
plain and ordinary meanings of the words used in the claim. See Johnson
Worldwide Assocs., Inc. v. Zebco Corp., 175 F.3d 985, 989–90 (Fed. Cir.
1999) (stating that “there must be a textual reference in the actual language
of the claim with which to associate a proffered claim construction”).
Nevertheless, as best as we can discern, Patent Owner’s claim
construction—however stated—focuses on two features of claim 1: (1) the
recitation of “a plurality of molecular targets,” and (2) the recitation of “a
listing of available therapeutic agents for each of the plurality of molecular
targets.” Specifically, Patent Owner argues:
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A POSA would understand that the patentee has chosen to
communicate the concept of cancer lineage-independence
through the selection of molecular targets not specific to any
specific type of cancer and the consideration of all potential
therapeutic agents regardless of the origin of the individual
patient’s cancer.
PO Resp. 32 (emphases added).
As to the molecular targets, it is undisputed that the plurality of
molecular targets (i.e., EGFR, KIT, TOP1, MLH1, PTEN, PDGFRA, and
ERBB2) recited in claim 1 were not associated with one particular type of
cancer in the prior art at the time of the ’365 patent.11 Ex. 2021 ¶ 55;
Ex. 2068, 26:24–27:21. Even so, that fact does not necessarily result in a
“cancer-lineage independent” system, because the remaining sections of
claim 1 do not require the identification of all available therapeutic agents,
including off-label therapeutic agents.
Put differently, the ’365 patent characterizes the disclosed system as
“identifying a non-specific disease therapy or agent capable of interacting”
with the molecular markers, i.e., an off-label therapeutic agent. Ex. 1001,
Abstract; id. at 14:8–12 (defining a “non-disease specific agent” as “a
therapeutic drug or compound not previously associated with treating the

11 We contrast Patent Owner’s arguments in this case with those in
IPR2019-00166, in which Patent Owner argued that a claim directed to “[a]
system for generating a report identifying a therapeutic agent for an
individual with lung cancer” was cancer-lineage independent because an
ordinarily skilled artisan would have recognized that the recited molecular
targets (i.e., PTEN, CTNNB1, cKIT, BRAF and PIK3CA) are not
traditionally associated with lung cancer. IPR2019-00166, Paper 29, 31.
Here, however, the preamble of claim 1 recites “an individual with a
cancer,” rather than a specific type of cancer.

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patient’s diagnosed disease” (emphasis added)).12 But nothing in the plain
language of sections (a)–(e) requires an identification of all available
therapeutic agents, i.e., both on-label and off-label therapeutic agents, for
those molecular markers. Instead, the plain language simply requires “a
listing of available therapeutic agents.” Ex. 1001, 17:16–17. Accordingly,
while claim 1 encompasses a system that is capable of identifying both on-
label and off-label therapeutic agents, claim 1 does not require the
identification of off-label therapeutic agents, and thus is not restricted to a
“cancer-lineage independent” approach.
And Patent Owner’s requirement—that the system be capable of
identifying all available therapeutic agents—cannot be read into the claim
from the written description, because the ’365 patent itself does not disclose
all the therapeutic agents there were available for certain molecular targets
as of May 18, 2006. Specifically, Table 1 of the ’365 patent purports to
present only “[s]ome of the non-disease specific agents that have been found
to interact with specific targets” such as EGFR (i.e., Erbitux™ and
Rapamycin™). Ex. 1001, 14:12–27. Moreover, it was known in the art, as
Dr. Spellman explains, that as of the earliest priority date of the ’365 patent,
other EGFR inhibitors were known, i.e., gefitinib (Iressa®) and erlotinib
(Tarceva®). Ex. 1002 ¶ 44 (citing Ex. 1009, 294; Ex. 1059, 107).
Finally, we agree with Petitioner that adding a “cancer lineage-
independence” requirement to claim 1 would result in some ambiguity,
given that the association of a particular molecular target with a particular
cancer changes over time. Reply 10–12. For example—and as Petitioner

12 Patent Owner agrees that an off-label therapeutic agent is one “not
. . . indicated for the patient’s cancer.” PO Sur-Reply 2.
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points out—Dr. O’Shaughnessy provided inconsistent answers to questions
about whether certain assays directed to the claimed molecular targets would
be “lineage independent” or “lineage dependent.” Compare Ex. 1119,
315:19–21 (testifying that “the only proven clinical utility of an EGFR
inhibitor was in lung cancer” in 2006), with id. at 338:18–339:1 (testifying
that it was not standard to check lung cancer for EGFR mutation in 2006);
compare id. at 317:16–18 (testifying that TOP1 is associated with colorectal
cancer), with id. at 318:12–14 (testifying that TOP1 “was definitely not
proven as a biomarker for colorectal cancer”). To add further confusion,
when asked whether the ’365 patent discloses “the lineage-independent
concept,” Dr. O’Shaughnessy testified during cross examination that “[i]t’s a
little hard to say ‘the lineage-independent concept,’ because that’s such a
broad way of stating it” and “I don’t know exactly what you mean by ‘the
lineage-independent concept.’” Id. at 452:2–13. Given these uncertainties,
we are disinclined to adopt Patent Owner’s argument that the claims require
a “cancer-lineage independent” approach.
In sum, we do not construe the claims to require the concept of
“cancer-lineage independence,” as Patent Owner argues. Despite any
support that might be otherwise present for such a requirement in the written
description, we are not persuaded that the claim language itself supports
Patent Owner’s construction. In determining the scope of the invention, “the
name of the game is the claim.” In re Hiniker Co., 150 F.3d 1362, 1369
(Fed. Cir. 1998). And here, consistent with its plain language, claim 1
requires a system for determining the molecular profile for an individual
with a cancer that generates a report identifying at least one therapeutic
agent indicating a likely benefit, based on that individual’s molecular
profile. We also determine that the claimed system may identify a cancer-
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lineage independent (i.e., off-label) therapeutic agent, but is not required to
do so.
D. Asserted References
Before turning to Petitioner’s asserted grounds of unpatentability, we
provide a brief summary of the asserted references.
1. Lu
Lu teaches a “computerized decision support system for selecting the
optimum treatment for human cancer.” Ex. 1004, (54). The system predicts
“which of one or more drugs suitable to treat a cancerous condition in a
patient are the optimum drug(s)” “based upon the particular patient’s
genotype.” Id. at (57). According to Lu, the system comprises:
a PCR kit and/or a gene chip designed to detect multiple genes,
expressions and/or mutations associated with a particular cancer
using a sample of the patient’s tissue or blood; a detector for
accepting receipt of the gene chip toward analyzing the patient’s
genotype; a database describing the correlation of patient
genotypes and the efficacy and toxicity of various anti-cancer
drugs used in treating patients with a particular cancerous
condition; and a computerized decision support system operably
connected to the detector for correlating the output of the detector
to the database.
Id. ¶ 18.
Lu teaches that the detector outputs genetic data into a “bioinformatic
software package” that compares the genetic data with “a database of data
toward providing the physician with a recommendation into plain English in
order to assist doctors to select the most effective medicine with the least
amount of side effects for patients.” Id. ¶ 42. Lu teaches that the software
may be “customized for a single disease or multiple diseases.” Id.
In a preferred embodiment, the system detects the breast cancer genes
ER Alpha, Her2, ErbB1, BRAC1, and BRAC2. Id. ¶ 22. For example, the
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system detects upregulation or downregulation of the expression of those
genes, or mutations in those genes. Id. ¶¶ 51, 53. Depending on the results,
the system provides an output that recommends or discourages the use of
certain drug(s) for cancer therapy. Id. ¶¶ 52, 54.
2. Illumina
Illumina is a technical bulletin prepared by Illumina, Inc. Ex. 1005.13
Illumina teaches that “[m]icroarray analysis of gene expression has proven
to be a remarkable tool,” but has faced challenges because of the lack of
high-quality and/or poor integrity RNA. Id. at 1 (Introduction). Illumina
discloses a “gene expression assay for microarrays that is capable of
utilizing partially degraded RNA.” Id.
Specifically, Illumina discloses the “cDNA-mediated Annealing,
Selection, extension and Litigation (DASL) Assay,” which “can monitor
RNA expression of up to 1536 sequence targets.” Id. According to
Illumina, “the DASL Assay offers researchers the opportunity to analyze
hundreds to thousands of RNA transcripts derived from previously collected,
preserved samples.” Id.
Illumina discloses a particular DASL assay—the “DASL Cancer
Panel”—that “is a pool of selected probe groups that targets 502 genes from
ten publicly available gene lists.” Id. at 4 (“The DASL Cancer Panel”).
Illumina teaches that the “[g]enes were chosen based on the frequency of

13 In its Preliminary Response, Patent Owner argued that Petitioner
had failed to establish that Illumina qualifies as a prior-art printed
publication. Prelim. Resp. 18–28. We discern that, following trial, Patent
Owner no longer pursues this argument. See generally PO Resp., PO Sur-
Reply. Based on the evidence of record, we determine that Petitioner has
met its burden of establishing that Illumina qualifies as a prior art printed
publication.
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appearance on these lists and the frequency of literature citations of these
genes in association with cancer.” Id. The DASL Cancer Panel includes,
among others, the genes EGFR, KIT, TOP1, MLH1, PTEN, PDGFRA, and
ERBB2. Id. at Table 1.
Illumina further teaches that the DASL assay can be used to analyze
differential expression profiles, and provides an example comparing the
expression of RNA from both normal prostate tissue and a prostate cancer
cell line. Id. at 5. Illumina states that “expression analysis using degraded
RNA will properly reflect biological differences using intact RNA.” Id. at 6.
Illumina also teaches the DASL assay can be used to study differences in
expression in clinical samples, to “report[] biologically relevant results.” Id.
at 7 (“Application to Clinical Samples”).
Finally, Illumina discloses that the DASL assay provides for high-
throughput expression profiling, because it allows for the analysis of 16 or
96 samples simultaneously. Id. at 8 (“Summary”).
3. Muraca
Muraca discloses a “system for accessing, organizing, and displaying
tissue information.” Ex. 1006 ¶ 1. The system “correlate[s] molecular
profiling data obtained from tissue microarrays with patient information in a
specimen-linked database.” Id. The specimen-linked database “is a
repository of information including . . . information relating to phenotype,
genotype, pathology, and expression of biomolecules in tissues, and
including information relating to the medical history of the individuals who
are the sources of tissues being analyzed,” such as demographic and
epidemiologic information. Id. ¶ 9.
Muraca teaches that, in one embodiment, the “system provides
information relating to diagnosis, prognosis, or likelihood of recurrence of a
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disease.” Id. ¶ 22. Specifically, a user inputs a patient’s biological
characteristic(s), such as gene or protein expression, into the system, which
then “retrieves information from the specimen-linked database about the
disease state associated with the particular expression pattern identified by
the user.” Id.
Muraca also teaches embodiments in which the system identifies drug
biological targets for drug therapy and potential drugs, provides information
relating to clinical trials, and suggests treatment options for a particular
disease diagnosis or prognosis. Id. ¶ 23.
4. McDoniels-Silvers
McDoniels-Silvers presents a study of the differential expression of
certain genes in human lung adenocarcinomas and squamous cell
carcinomas compared to normal lung tissues. Ex. 1007, Abstract.
McDoniels-Silvers examined the expression of 588 genes using a human
cDNA expression array. Id. McDoniels-Silvers obtained tumor tissue
samples from cancer patients, and compared the results to normal tissues.
Id. at 142. McDoniels-Silvers found that 45 of those genes “were
differentially expressed by at least two-fold in tumor tissues compared to
corresponding normal tissues.” Id. at 141. McDoniels-Silvers teaches that
“[t]hese gene expression changes may directly contribute to the initiation or
progression of human lung cancer or may be secondary effects of the
tumorigenesis process,” but “[r]egardless, many of these differences may be
useful in the diagnosis and/or treatment of” lung cancers. Id.
E. Obviousness over Lu in View of Illumina
Petitioner contends that claims 1–14 are unpatentable as having been
obvious over Lu in view of Illumina. Pet. 23–59. Patent Owner opposes.
PO Resp. 35–50; PO Sur-Reply 20–25. Having considered the totality of the
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arguments and evidence, we find that Petitioner has shown by a
preponderance of the evidence that claims 1–14 are unpatentable as having
been obvious over Lu in view of Illumina.
1. Limitations of the challenged claims
Petitioner contends that the combination of Lu and Illumina teaches or
suggests each element of the challenged claims. Petitioner presents
arguments mapping the language of claims 1–14 to the disclosures of each
reference. Pet. 23–49. We have reviewed Petitioner’s arguments and, for
the reasons articulated below, find that a preponderance of the evidence
supports Petitioner’s contentions.
a) Claim 1
Claim 1 recites, in the preamble, a “system for generating a report
identifying at least one therapeutic agent for an individual with a cancer.”
Ex. 1001, 17:5–6. We agree with Petitioner that Lu teaches this portion of
the claim by disclosing:
It is [one] object of the present invention to identify which drugs
are optimum to treat other cancerous conditions in patients. It is
another object of the present invention to provide a computerized
decision support system to provide in plain language to a
physician a recommendation as to the optimum anti-cancer drug
to prescribe for a patient.
Ex. 1004 ¶¶ 15–16; see also Pet. 23 (citing Ex. 1002 ¶ 124). Lu teaches that
the “recommendation” may be in the form of a printed-out report, thus
teaching “generating a report.” See Ex. 1004 ¶ 45 (“Report processor 47
provides the computer analysis from the optimization processor 46 in a
printout form 49 or on a computer screen 19.”); see also id. at Fig. 4
(referring to printout form 49 as the “Final Report”).
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Next, in section (a), claim 1 recites “at least one device configured to
assay a plurality of molecular targets in a biological sample to determine
molecular profile test values for the plurality of molecular targets, wherein
the plurality of molecular targets comprises EGFR, KIT, TOP1, MLH1,
PTEN, PDGFRA and ERRB2.” Ex. 1001, 17:7–12. We agree with
Petitioner that “Lu and Illumina disclose this limitation in combination.”
Pet. 24 (citing Ex. 1002 ¶¶ 125–130).
Specifically, Lu “discloses a PCR kit and/or a gene chip designed to
detect multiple genes, expressions and/or mutations . . . using a sample of
the patient’s tissue or blood.” Ex. 1004 ¶¶ 18, 19, 22; Pet. 24–25. Lu
discloses that multiple targets can be assayed by, for example, RT-PCR, and
that the assays “produce test values” in the form of up-regulation or down-
regulation data. Ex. 1004 ¶¶ 34, 35, 51, 52; Ex. 1002 ¶ 125. Lu discloses
assaying the genes EGFR (also known as ERBB114) and HER2 (also known
as ERBB215) and but does not disclose the remaining genes recited in claim
1. Ex. 1004 ¶¶ 22, 48, 51, 53, 54; Pet. 18–19 (citing Ex. 1002 ¶¶ 100).
Illumina, however, discloses the DASL Cancer Panel, which allows
the determination of expression values for up to 1536 nucleic acid sequence
targets that correspond to 502 cancer-related genes. Ex. 1005, 1, 3; Pet. 25
(citing Ex. 1002 ¶ 126). Such targets include, as Petitioner points out, the
genes EGFR, ERBB2, KIT, TOP1, MLH1, PTEN, and PDGFRA. Ex. 1005,
4 (Table 1); Pet. 26–27 (citing Ex. 1002 ¶ 127). Thus, taken together, Lu
and Illumina recite the molecular targets recited in claim 1.

14 See Ex. 1044 (describing “ERBB1” as a synonym of “EGFR”).
15 See Ex. 1045 (describing “ERBB2” as a synonym of “HER2”).
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Claim 1 recites in section (b) “at least one computer database
comprising: i. a reference value for each of the plurality of molecular targets;
and ii. a listing of available therapeutic agents for each of the plurality of
molecular targets.” Ex. 1001, 17:13–17. We agree with Petitioner that Lu
discloses a computer database with biological profile data that includes
reference values for molecular targets and a listing of available therapeutic
agents for the molecular targets. Pet. 28–32. Specifically, Lu discloses a
“computerized decision support system” that comprises “a database.”
Ex. 1004 ¶ 18, Fig. 4 (disclosing “Gene & Drug Database” 42). Lu explains
that the gene and drug database stores “criteria and drug information” to
which the expression levels of molecular targets are compared to determine,
e.g., upregulation or downregulation. Id. ¶¶ 18, 50, 51; Pet. 29–30 (citing
Ex. 1002 ¶ 132). Lu also discloses that the gene and drug database is
updated “as new drugs are developed and as existing drugs are used more
and more.” Ex. 1004 ¶¶ 4, 44. Thus, we agree with Petitioner that this
disclosure satisfies the claim limitation of “a listing of available therapeutic
agents for each of the plurality of molecular targets.” Pet. 31–32 (citing
Ex. 1002 ¶ 135).
We also agree with Petitioner that Illumina discloses comparing test
expression values derived from a cancerous sample to reference values from
a normal sample. Id. at 30–31 (citing Ex. 1002 ¶¶ 133–134). For example,
in Figure 4, Illumina provides a comparison of the expression data of normal
prostrate cells to LNCaP cells, a prostate cancer cell line. Ex. 1005, 5 (Fig.
4); see also id. at 6–7 (Fig. 6 (comparing expression values from prostrate
and colon cancer samples to normal tissues)).
Next, claim 1 recites in section (c) “a computer-readable program
code comprising instructions to input the molecular profile test values and to
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compare each of the molecular profile test values with a corresponding
reference value from the at least one computer database in (b)(i).” Ex. 1001,
17:18–22. We agree with Petitioner that Lu discloses this limitation.
Pet. 32–33 (citing Ex. 1002 ¶ 136). Lu discloses that the database
“correlat[es] . . . patient genotypes and the efficacy and toxicity of various
anti-cancer drugs . . . with a particular cancerous condition,” and that the
“computerized decision support system” “correlat[es] the output of the
detector to the database.” Ex. 1004 ¶ 18. Specifically, the system “serves to
correlate and calculate the raw signals/data provided . . . and will interpret
the raw signals/data according to criteria and drug information stored in the
system database.” Id. ¶ 50.
Claim 1 further recites in section (d):
a computer-readable program code comprising instructions to
access the at least one computer database and to identify at least
one therapeutic agent from the listing of available therapeutic
agents for the plurality of molecular targets wherein the
comparison to the reference values in (c) indicates a likely
benefit of the at least one therapeutic agent.
Ex. 1001, 17:23–29. We agree with Petitioner that Lu teaches this limitation
by disclosing:
a database which associates patient genotypes and the efficacy
and toxicity of various anti-cancer drugs used in treating patients
with a particular cancerous condition connected to the detector
[that] correlates the output of the detector to the database to
provide a recommendation as to which drugs are optimum for
treating the patient’s cancer.
Ex. 1004, Abstract; see also id. ¶ 38. Lu also teaches an “optimization
processor” that “consists of a number of search algorithms that find the best
fit results for the patient using the knowledge contained in the . . . gene and
drug databases,” and “provides [a] computer analysis” to determine “the
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optimum drugs based upon a patient genotype.” Id. ¶¶ 45–46; Pet. 36–37
(citing Ex. 1002 ¶ 143). The computer analysis may list the benefits of the
drug as well as its side effects. Ex. 1004 ¶¶ 45–46.
Finally, claim 1 recites in section (e) “a computer-readable program
code comprising instructions to generate a report that comprises a listing of
the molecular targets for which the comparison to the reference value
indicated a likely benefit of the at least one therapeutic agent in (d) and the
at least one therapeutic agent identified in (d).” Ex. 1001, 17:30–35.
Petitioner asserts that Lu discloses the creation of a patient profile report that
includes test results for various targets and proposed therapies. Pet. 37–38
(citing Ex. 1002 ¶¶ 144–145).16 We agree. Specifically, Lu’s system
comprises report processor software that “provide[s] the physician with the
plain language recommendation as to which drugs to use for a particular
patient.” Ex. 1004 ¶¶ 44–45. In Figure 4, Lu shows the “recommendation”
in the form of a printed-out “final report” 49. Id. (Fig. 4). Lu discloses
sample listings of raw signals or data generated by the system detector, id.
¶¶ 51, 53, and teaches that the “bioinformatic software program correlate[s]
and calculate[s]” that data with the genetic and drug database, to result in a
“plain spoken language” report, id. ¶¶ 50, 52, 54.
We are not persuaded by Patent Owner’s arguments that the
combination of Lu and Illumina fails to teach the limitations of claim 1. PO

16 Petitioner also asserts that this limitation is not entitled to patentable
weight because it is directed to the content of information and lacks a
requisite functional relationship (i.e., is non-functional descriptive material).
Pet. 37 (citing Praxair Distribution, Inc. v. Mallinckrodt Hosp., Prods. IP
Ltd., 890 F.3d 1024, 1032 (Fed. Cir. 2018)). We need not resolve this issue,
because for the reasons described above, we are satisfied that Lu teaches this
limitation.
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Resp. 35–45; PO Sur-Reply 21–25. Patent Owner argues that “even if Lu
and Illumina could be combined, the resulting combination would lack a key
element of the claims, namely, a system that identifies a therapeutic agent
for a cancer patient independent of cancer lineage.” PO Resp. 35. But, as
explained in detail above, we do not read the claims as requiring that the
claimed system is “cancer-lineage independent.” Supra § II.C.3.
Specifically, under our construction, the system of claim 1 may
identify a cancer-lineage independent (i.e., off-label) therapeutic agent, but
is not required to do so. Id. Patent Owner conceded at the oral hearing that,
if we construed the claims as encompassing a “lineage dependent analysis,”
then the prior art taught the claimed subject matter. Tr. 35:15–36:12.
Specifically, Patent Owner concedes that Lu teaches the identification of
“various anti-cancer drugs used in treating patients with a particular
cancerous condition,” i.e., on-label therapeutic agents. PO Resp. 37
(quoting Ex. 1004 ¶ 18 (emphasis omitted)).
But even if we read claim 1 as requiring a cancer-lineage independent
approach (i.e., one in which both the molecular markers are not associated
with any one particular cancer and the system must be capable of identifying
off-label therapeutic agents), we still find that the combination of Lu and
Illumina discloses or suggests each and every limitation of claim 1.
First, Illumina’s microarray of molecular targets is clearly “pan-
cancer” and, thus, “cancer-lineage independent,” as Patent Owner uses that
term in its arguments. Specifically, Illumina discloses the DASL Cancer
Panel, which allows for the determination of expression values for up to
1536 nucleic acid sequence targets that correspond to 502 cancer-related
genes. Ex. 1005, 1, 3; Pet. 26–27 (citing Ex. 1002 ¶ 127). Illumina teaches
that the panel can detect molecular targets associated with a wide variety of
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cancers, including at least prostate, colon, and breast cancers. Ex. 1005, 5–
8; Ex. 1120 ¶ 65; Reply 19–20. Illumina’s molecular targets include EGFR,
KIT, TOP1, MLH1, PTEN, PDGFRA, and ERBB2—each and every
molecular target listed in claim 1. Ex. 1005, 4 (Table 1); Pet. 26–27 (citing
Ex. 1002 ¶ 127); see also Ex. 1119, 401:11–403:11 (testimony of Dr.
O’Shaughnessy that Illumina’s DASL panel includes all the claimed
molecular targets). Thus, as Patent Owner describes its listing of molecular
targets as “pan-cancer” and “cancer-lineage independent,” so too is
Illumina’s listing of molecular targets. See PO Resp. 28 (arguing that,
because “a POSA reading the group of molecular targets identified in section
(a) of claim 1 would recognize that it is not directed at any one specific type
of cancer,” they are a “lineage-independent group”).
That Illumina discloses a “cancer-lineage independent” panel of
molecular targets is also well supported by the testimony of both
Dr. O’Shaughnessy and Dr. Spellman. See Ex. 1119, 333:3–20 (“Q. And
it’s also your opinion that the panel . . . contain[ing] those seven targets [of
claim 1] is necessarily lineage independent, correct? A. (Dr.
O’Shaughnessy) Yes.”); id. at 426:16–21 (testimony of Dr. O’Shaughnessy
that “there are genes on the Illumina set that come from a wide variety of
cancers”); id. at 439:1–3 (testimony of Dr. O’Shaughnessy that the DASL
assay can analyze many targets in one assay); Ex. 1118, 202:3–22
(testimony of Dr. O’Shaughnessy that “microarrays were built” to “assay a
wide variety of genes” simultaneously); Ex. 1120 ¶¶ 64–66 (Dr. Spellman’s
declaration testimony).
Second, even if the “cancer-lineage independent” system must be
capable of identifying off-label therapeutic agents, we find that Lu teaches
this requirement, or that, at minimum, the combination of Lu and Illumina
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suggests this requirement to an ordinarily skilled artisan. Although Patent
Owner argues that Lu is limited to identifying therapeutic agents “from a
database of drugs known to treat that particular cancer,” PO Resp. 38–39
(emphasis omitted), we find that Lu’s disclosure is broader than that.
Specifically, Lu generally teaches that its system can be used “to
predict or identify the optimum drug for treating cancers other th[a]n breast
cancer,” and “can be used to identify an optimum drug for treating virtually
any disease for which there exists an established correlation between a
patient genotype and the efficacy and toxicity of each of a group of drugs
developed to treat the general condition.” Ex. 1004 ¶ 56 (emphases added).
Lu also teaches that the effectiveness of a particular drug can vary “from
patient to patient”—even patients within the same patient group. Id. ¶ 3.
And Lu teaches that “there exists a known database” of therapeutic agents
“developed typically through clinical trial,” and that “as new drugs are
developed and existing drugs are used more and more, the database grows.”
Id. ¶ 4.
We find that these disclosures provide a preponderance of evidence
that supports Petitioner’s position (and Dr. Spellman’s testimony) that Lu’s
system is capable of determining therapeutic agents based on the individual
patient’s genotype, and therefore is not limited to drugs indicated for that
patient’s particular cancer type (i.e., on-label therapeutic agents). See
Ex. 1004 ¶ 10 (“Accordingly, it is an object of the present invention to
provide a system which can be used by doctors to identify which
pharmaceutical drugs from among several potential choices is indeed the
most appropriate to treat a patient’s particular medical condition.”); id. ¶ 46
(describing presentation of “recommendations as to the optimum drugs
based upon a patient genotype to the doctor in an understandable manner”);
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id. ¶ 47 (describing “diagnostic software program with accompanying
database for prediction of gene and drug interaction”); see also Ex. 2068,
146:18–147:1 (Dr. Spellman’s testimony); Ex. 1120 ¶¶ 55–63.
At a minimum, we find that the combination of Lu and Illumina
suggests to an ordinarily skilled artisan a system capable of identifying off-
label therapeutic agents. We find credible, and supported with preponderant
record evidence, Dr. Spellman’s unrebutted testimony that an ordinarily
skilled artisan would have understood molecular profiling to have been a
recognized method for identifying therapeutic agents, irrespective of a
patient’s particular disease, before the May 16, 2006, effective filing date of
the ’365 patent. Ex. 1002 ¶¶ 35–46.
Specifically, Dr. Spellman provides evidence that, by the early 2000s,
“microarrays were widely used in genomics-based research to predict drug
response based on gene expression profiles.” Id. ¶ 64 (citing Ex. 1026,
10787 (stating that DNA microarrays “permit the simultaneous measurement
of the expression levels of thousands of genes, rais[ing] the possibility of an
unbiased, genomewide approach to the genetic basis of drug response”).
Dr. Spellman also provides evidence that “[c]ommercial microarrays with
many thousands of genes on a single device were widely available” as of the
early 2000s. Id. ¶¶ 65–66 (citing Ex. 1027; Ex. 1028). As Dr. Spellman
explains, these arrays provided the “ability to screen hundreds to thousands
of potential targets in a single experiment.” Id. ¶ 66.
Dr. Spellman also provides evidence that, before 2006, various
databases providing reference values for the expression of molecular targets,
as well as databases correlating known drug targets and their respective
drugs, were also well known in the art. Id. ¶¶ 68–74, 76–80 (describing the
ONCOMINE databases (Exs. 1030–32), the ArrayExpress database
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(Ex. 1033), the Stanford Microarray Database (Ex. 1034), the TRMP
(“Therapeutically Relevant Multiple Pathways”) database (Ex. 1036), the
TTD (“Therapeutic Target Database”) (Ex. 1037), and the Cosmic (“Catalog
of Somatic Mutations in Cancer”) database (Ex. 1038)).
We agree with Dr. Spellman that, given the state of the art, an
ordinarily skilled artisan would have understood that the combination of
Illumina’s microarray of molecular targets and Lu’s database of therapeutic
agents would suggest the identification of off-label therapeutic agents. See
Ex. 1120 ¶¶ 52–54. As noted above, Lu teaches the use of existing
databases of therapeutic agents “developed typically through clinical trial,”
and that “as new drugs are developed and existing drugs are used more and
more, the database grows.” Ex. 1004 ¶ 4.
Patent Owner argues that Lu’s database would be limited to
therapeutic agents already known to be useful for treating a patient’s
particular disease—i.e., on-label drugs. PO Resp. 38–39. We disagree. The
prior-art TRMP, TTD, and Cosmic databases were well-known,
commercially-available databases that listed therapeutic agents for a wide
variety of molecular targets, regardless of disease type. Ex. 1002 ¶¶ 76–80;
Ex. 1036; Ex. 1037; Ex. 1038. It would make little sense for the ordinarily
skilled artisan to remove from those databases references to any off-label
therapeutic agents for a patient’s particular disease, especially given that
Patent Owner has conceded that that artisan would have been motivated to
replace Lu’s microarray with Illumina’s DASL assay, as explained below.
See Tr. 54:14–55:8; see also infra § II.E.2.a. We also emphasize that claim
1 is directed to a system for identifying a therapeutic agent; there is no
requirement that the identified therapeutic agent be used in a method for
treating an individual with cancer.
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In sum, we determine that Petitioner has shown, by a preponderance
of the evidence, that the combination of Lu and Illumina teaches or suggests
each and every limitation of claim 1.
b) Dependent claims 2–14
Having decided that the combination of Lu and Illumina teaches or
suggests each and every limitation of claim 1, we turn to the remaining
claims of the ’365 patent, which are all directly dependent on claim 1 (i.e.,
claims 2–14). We find that Petitioner also shows by a preponderance of the
evidence that Lu and Illumina account for the limitations in these claims.
Pet. 38–49. We have also reviewed Dr. Spellman’s testimony and find that a
preponderance of the evidence supports his contention that the cited
references collectively disclose or suggest each and every limitation of
claims 2–14. See Ex. 1002 ¶¶ 146–147 (claim 2) (citing Ex. 1004 ¶¶ 4, 23;
Ex. 1037, Abstract; Ex. 1055, Abstract, D671); id. ¶¶ 148–149 (claim 3)
(citing Ex. 1004, Abstract; Ex. 1037, Abstract; Ex. 1055, Abstract, D671);
id. ¶¶ 150–151 (claim 4) (citing Ex. 1004 ¶ 45, Fig. 4); id. ¶¶ 152–153
(claim 5) (citing Ex. 1004 ¶¶ 23, 36, 37, 42–44, 47, 50); id. ¶¶ 154–156
(claim 6) (citing Ex. 1004 ¶¶ 18, 38, 42, 50–54; Ex. 1005, 3, 7, Figs. 4, 6, 7);
id. ¶¶ 157–159 (claim 7) (citing Ex. 1004 ¶¶ 43, 46; Ex. 1056, 667, 668;
Ex. 1047, 2386); id. ¶¶ 160–162 (claim 8) (citing Ex. 1004, Abstract, ¶¶ 18–
20, 31–33, 47, 49, Fig. 2, claims 2 and 7; Ex. 1005, 5–8); id. ¶¶ 163–165
(claim 9) (citing Ex. 1004, Abstract, ¶¶ 18, 19, 34, 36, 51, 53; Ex. 1005, 1, 4,
6–8, Fig. 7); id. ¶¶ 166–169 (claim 10) (citing Ex. 1005, 5, 7, 8, Figs. 4, 6–
8); id. ¶¶ 170–172 (claim 11) (citing Ex. 1004 ¶¶ 43, 46; Ex. 1056, 667–668;
Ex. 1047, 2386); id. ¶¶ 173–175 (claim 12) (citing Ex. 1004 ¶¶ 18, 32, 33,
36; Ex. 1005, 1, 4, 7); id. ¶¶ 176–178 (claim 13) (citing Ex. 1004, Abstract,
¶¶ 18, 32, 33, 36, 37; Ex. 1005, 1); id. ¶¶ 179–181 (claim 14) (citing
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Ex. 1004, Abstract, ¶¶ 18, 19, 34, 36, 51, 53; Ex. 1005, 1, 4, 7, Fig. 7).
Patent Owner does not present separate arguments for any of the dependent
claims. See generally PO Resp. 36–45. We, therefore, adopt the teachings
set forth in the Petition and in Dr. Spellman’s Declaration as mapped to the
limitations of the challenged claims as our own findings. See In re
NuVasive, Inc., 841 F.3d 966, 974 (Fed. Cir. 2016) (explaining that the
Board need not make specific findings about claim limitations that a patent
owner does not dispute are disclosed in the prior art); see also Ex. 1002
¶ 182 (Dr. Spellman’s claim chart).
2. Motivation to combine/reasonable expectation of success
Even “[i]f all elements of the claims are found in a combination of
prior art references,” “the factfinder should further consider whether a
person of ordinary skill in the art would [have been] motivated to combine
those references, and whether in making that combination, a person of
ordinary skill would have [had] a reasonable expectation of success.” Merck
& Cie v. Gnosis S.P.A., 808 F.3d 829, 833 (Fed. Cir. 2015). The
“motivation to combine” and “reasonable expectation of success” factors are
subsidiary requirements for obviousness subsumed within the Graham
factors. Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1361 (Fed. Cir. 2007).
We address motivation to combine and reasonable expectation of success in
turn below.
a) Motivation to combine
Petitioner contends that an ordinarily skilled artisan would have had a
reason to combine the teachings of Lu and Illumina, with a reasonable
expectation of success, based on the teachings of the art, and based on the
Lu and Illumina references themselves. Pet. 49–55. In our Institution
Decision, we determined that Petitioner had shown sufficiently for
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institution that an ordinarily skilled artisan would have been motivated to
modify Lu’s system with Illumina’s DASL assay. Inst. Dec. 17–19. Upon
review of the complete record, we affirm our initial determination. We find
that the preponderance of record evidence supports Petitioner’s argument
that an ordinarily skilled artisan would have regarded RT-PCR assays as old
technology, readily replaced by the more advanced DASL assay. Pet. 52–
53; Ex. 1002 ¶ 118–119. We also rely on and credit Dr. Spellman’s
testimony that the DASL assay was “capable of investigating a substantially
larger number of molecular targets simultaneously than RT-PCR.” Ex. 1002
¶ 119; see also Ex. 1047, 2386; Ex. 1053, 586; Pet. 52–55. In view of this
evidence, we find that a preponderance of the evidence supports that an
ordinary artisan would have been motivated to modify Lu’s system with
Illumina’s DASL assay. We note that, during oral hearing, counsel for
Patent Owner conceded that an ordinarily skilled artisan would have been
motivated to use Illumina’s DASL assay in Lu’s system:
JUDGE: . . . [W]hy wouldn’t somebody skilled in the art just
replace the chip, that Lu talks about, with a DASL assay chip?
. . .
MR. SINGER: . . . I think they have the better of the argument,
there, to be perfectly blunt, that people would go to something
that was a commercial product and use it. So, I will acknowledge
that . . . .
Tr. 54:15–55:8.
b) Reasonable expectation of success
We next consider whether Petitioner has shown by a preponderance of
the evidence that the skilled artisan would have had a reasonable expectation
of success in achieving the method claimed in the ’365 patent. “The
reasonable expectation of success requirement refers to the likelihood of
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success in combining references to meet the limitations of the claimed
invention.” Intelligent Bio-Sys., Inc. v. Illumina Cambridge Ltd., 821 F.3d
1359, 1367 (Fed. Cir. 2016).
We are persuaded that Petitioner has shown by a preponderance of the
evidence that an ordinarily skilled artisan would have had a reasonable
expectation of success using Illumina’s DASL assay in Lu’s system, given
that the DASL assay was commercially available and recognized in the art
as useful for high-throughput expression analysis. See Pet. 55–59; see also
Ex. 1002 ¶¶ 183–187; Ex. 1050, 28–31; Ex. 1046, 2; Ex. 1048, 1806;
Ex. 1049, 878. We also observe that all the elements of molecular profiling
systems were known, and required only ordinary skill to carry out. See
Pet. 57–59; see also Ex. 1002 ¶ 68, 186; Ex. 1037, Abstract; Ex. 1055,
Abstract; Ex. 1051, 170, 172; Ex. 1032, 166, 169 (Table 2). Patent Owner
does not provide specific arguments disputing Petitioner’s position as to
reasonable expectation of success. See generally PO Resp.; PO Sur-Reply;
see also Reply 21 n.12.
3. Objective indicia of non-obviousness
We must consider any evidence of objective indicia of non-
obviousness before reaching our conclusion on obviousness vel non. WBIP,
LLC v. Kohler Co., 829 F.3d 1317, 1328 (Fed. Cir. 2016). Notwithstanding
what the teachings of the prior art would have suggested to one of ordinary
skill in the art at the time of the invention, the totality of the evidence
submitted, including objective evidence of non-obviousness, may lead to a
conclusion that the challenged claims would not have been obvious to one of
ordinary skill. In re Piasecki, 745 F.2d 1468, 1471–72 (Fed. Cir. 1984).
Patent Owner presents evidence of three of these considerations: (1) long-
felt need, (2) skepticism/surprise (3) praise. PO Resp. 48–50.
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a) Nexus
At the outset, we give Patent Owner’s arguments about long-felt need
and praise very little to no weight in our obviousness analysis. “For
objective evidence of secondary considerations to be accorded substantial
weight, its proponent must establish a nexus between the evidence and the
merits of the claimed invention.” In re Huai-Hung Kao, 639 F.3d 1057,
1068 (Fed. Cir. 2011) (quotation and emphasis omitted); see also Fox
Factory, Inc. v. SRAM, LLC, 944 F.3d 1366, 1373 (Fed. Cir. 2019) (“In
order to accord substantial weight to secondary considerations in an
obviousness analysis, the evidence of secondary considerations must have a
nexus to the claims, i.e., there must be a legally and factually sufficient
connection between the evidence and the patented invention.” (quotation
omitted)).
Here, Patent Owner also does not allege (or even mention) a “nexus”
in its Response. See PO Resp. 14–24, 48–50. And this is not a case where
we apply a presumption of nexus, because Patent Owner has not shown or
alleged a specific product that is the invention disclosed and claimed in the
’365 patent. Id.; see also WBIP, 829 F.3d at 1329 (setting forth
circumstances in which the presumption of nexus applies); Fox Factory, 994
F.3d at 1373 (explaining that a nexus is presumed when “the patentee shows
that the asserted objective evidence is tied to a specific product and that
product ‘embodies the claimed features, and is coextensive with them.’”
(quoting Polaris Indus., Inc. v. Arctic Cat, Inc., 882 F.3d 1056, 1072 (Fed.
Cir. 2018))).
In addition to a lack of nexus to the claimed invention, Patent Owner
also fails to provide specific, persuasive evidence of long-felt need beyond a
conclusory statement that “Drs. Von Hoff and Penny’s invention
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fulfilled a long-felt need in the oncology community for improved tools for
identifying therapeutic agents for their cancer patients.” PO Resp. 48. This
statement falls short of a preponderance of evidence that the claimed
invention fulfills a long-felt need.
b) Bisgrove trial
In its Sur-Reply, Patent Owner alleges a nexus between the claims and
the Bisgrove trial. PO Sur-Reply 25–28 (citing Ex. 201317). Specifically,
Patent Owner argues that “[t]he Bisgrove trial and its preceding abstract are
strongly tied to the claimed system of the ’365 patent.” Id. at 26. According
to Patent Owner, the “the oncology community initially expressed
skepticism of the invention when it was first reported.” PO Resp. 48. And it
was not until the Bisgrove trial, “which Drs. Von Hoff and Penny conducted
to gather clinical evidence in the face of that skepticism,” Patent Owner
argues, that the inventors “surprisingly demonstrated that their system
worked.” Id. at 48–49.
Although we have carefully considered Patent Owner’s arguments and
evidence, we again find that they fail to show nexus to the claimed
invention. For example, Patent Owner argues that Drs. Von Hoff and Penny
conducted the Bisgrove trial “using a treatment regimen selected by cancer-
lineage independent molecular profiling of the patient’s tumor.” PO Resp.
17–18 (citing Ex. 2021 ¶¶ 37, 39). But Patent Owner fails to provide
specific, persuasive evidence showing that the therapeutic agents used in the
Bisgrove trial were, in fact, selected by a system embodied in the claims of

17 Daniel D. Van Hoff et al., Pilot Study Using Molecular Profiling of
Patients’ Tumors to Find Potential Targets and Select Treatments for Their
Refractory Cancers, 28 (33) J. CLIN. ONCOL. 4877–83 (Nov. 20, 2010) (“the
Bisgrove trial”) (Ex. 2013).
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the ’365 patent. See id.; see also PO Sur-Reply 25–27 (citing Ex. 2021
¶¶ 42–45). For example, neither Patent Owner nor Dr. O’Shaughnessy
explain how Drs. Von Hoff and Penny used the limitations of claim 1 (e.g., a
device, computer database, and computer-readable program codes) to
generate a report comprising a list of molecular targets and therapeutic
agents. See PO Resp. 48–49; PO Sur-Reply 26–27; Ex. 2021 ¶¶ 37–40.
We also find Patent Owner’s arguments and evidence insufficient to
support skepticism and surprise. For example, Patent Owner relies on
Dr. O’Shaughnessy’s declaration as evidence of skepticism of the Bisgrove
trial. PO Resp. 48–49 (citing Ex. 2021 ¶¶ 42–44). But during cross-
examination, Dr. O’Shaughnessy admitted she cited no contemporaneous
evidence for her opinion that oncologists were skeptical of the alleged
invention, could not recall how many doctors she spoke with about the
claimed invention, and could not answer how many of those doctors
expressed skepticism. Ex. 1118, 210:2–212:20. We find that this testimony
of Dr. O’Shaughnessy, many years after the fact and without corroboration,
is entitled to little weight. See Rohm & Haas Co. v. Brotech Corp., 127 F.3d
1089, 1092 (Fed. Cir. 1997) (“Nothing in the rules or in our jurisprudence
requires the fact finder to credit the unsupported assertions of an expert
witness.”).
For these reasons, we are not persuaded by Patent Owner’s arguments
that skepticism and surprise weigh toward the non-obviousness of the
claimed subject matter.
4. Conclusion as to obviousness over Lu in view of Illumina
In sum, we find that the combination of Lu and Illumina teaches or
suggests each and every element of claims 1–14. We find that an ordinarily
skilled artisan would have been motivated to combine Lu with Illumina, and
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would have had a reasonable expectation of success in achieving the claimed
invention. We also find that Patent Owner has failed to persuasively show
secondary considerations of non-obviousness. As discussed above, we find
that Patent Owner has not established the requisite nexus between the
challenged claims and any of the asserted secondary considerations. We are
therefore unable to accord them any substantial weight. Fox Factory, 944
F.3d at 1373. Thus, after carefully considering the arguments and evidence,
we determine that the record as a whole weighs in favor of a conclusion of
obviousness, especially given the disclosures of the art of record in this case
and strength of the obviousness case based on the first three Graham factors.
F. Petitioner’s Remaining Grounds of Unpatentability
Our determination that Petitioner has demonstrated, by a
preponderance of the evidence, that claims 1–14 would have been obvious
over Lu and Illumina involves all challenged claims of the ’365 patent.
Thus, we need not address Petitioner’s grounds of unpatentability based on
obviousness of claims 2 and 3 over Lu, Illumina, and Muraca, Pet. 59–65, or
obviousness of claims 7 and 11 over Lu, Illumina, and McDoniels-Silvers,
Pet. 65–66. See, e.g., Nippon Suisan Kaisha Ltd. v. Pronova Biopharma
Norge AS, PGR2017-00033, Paper 37 at 27 (PTAB Jan. 16, 2019) (citing
SAS Inst. Inc. v. Iancu, 138 S. Ct. 1348, 1359 (2019) (holding that a
petitioner “is entitled to a final written decision addressing all of the claims
it has challenged”); Beloit Corp. v. Valmet Oy, 742 F.2d 1421, 1423 (Fed.
Cir. 1984) (holding that once a dispositive issue is decided, there is no need
to decide other potentially dispositive issues)).

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III. CONCLUSION18
Petitioner establishes by a preponderance of the evidence that claim
1–14 of the ’365 patent are unpatentable as follows.

18 Should Patent Owner wish to pursue amendment of the challenged
claims in a reissue or reexamination proceeding subsequent to the issuance
of this decision, we draw Patent Owner’s attention to the April 2019 Notice
Regarding Options for Amendments by Patent Owner Through Reissue or
Reexamination During a Pending AIA Trial Proceeding. See 84 Fed. Reg.
16,654 (Apr. 22, 2019). If Patent Owner chooses to file a reissue application
or a request for reexamination of the challenged patent, we remind Patent
Owner of its continuing obligation to notify the Board of any such related
matters in updated mandatory notices. See 37 C.F.R. § 42.8(a)(3), (b)(2).

19, 20 As explained above, we do not reach these alleged grounds of
unpatentability. Supra § II.F.

Claims

35 U.S.C.
§
Reference(s)/Basis Claims
Shown
Unpatentable
Claims
Not Shown
Unpatentable
1–14 103(a) Lu, Illumina 1–14
2, 3 103(a)19 Lu, Illumina,
Muraca

7, 11 103(a)20 Lu, Illumina,
McDoniels-Silvers

Overall
Outcome
1–14
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IV. ORDER
In consideration of the foregoing, it is hereby:
ORDERED that claims 1–14 of the ’365 patent have been proven to
be unpatentable; and
FURTHER ORDERED that because this is a Final Written Decision,
parties to the proceeding seeking judicial review of the Decision must
comply with the notice and service requirements of 37 C.F.R. § 90.2.

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FOR PETITIONER:
David L. Cavanaugh
William W. Kim
Kevin M. Yurkerwich
Eric Ross Cohen
WILMER CUTLER PICKERING HALE AND DORR LLP
david.cavanaugh@wilmerhale.com
william.kim@wilmerhale.com
kevin.yurkerwich@wilmerhale.com
ross.cohen@wilmerhale.com

FOR PATENT OWNER:
Dorothy Whelan
Mike Kane
Martina Hufnal
FISH & RICHARDSON P.C.
whelan@fr.com
kane@fr.com
hufnal@fr.com