Guardant Health, Inc. v. Vidal ( 2023 )

Case: 21-1104 Document: 42 Page: 1 Filed: 05/05/2023
NOTE: This disposition is nonprecedential.
United States Court of Appeals
for the Federal Circuit
______________________
GUARDANT HEALTH, INC.,
Appellant
v.
KATHERINE K. VIDAL, UNDER SECRETARY OF
COMMERCE FOR INTELLECTUAL PROPERTY
AND DIRECTOR OF THE UNITED STATES
PATENT AND TRADEMARK OFFICE,
Intervenor
______________________
2021-1104
______________________
Appeal from the United States Patent and Trademark
Office, Patent Trial and Appeal Board in No. IPR2019-
00652.
______________________
Decided: May 5, 2023
______________________
MICHAEL T. ROSATO, Wilson, Sonsini, Goodrich &
Rosati, PC, Seattle, WA, argued for appellant. Also repre-
sented by SONJA ROCHELLE GERRARD; RICHARD TORCZON,
Washington, DC.
SARAH E. CRAVEN, Office of the Solicitor, United States
Patent and Trademark Office, Alexandria, VA, argued for
Case: 21-1104 Document: 42 Page: 2 Filed: 05/05/2023
2 GUARDANT HEALTH, INC. v. VIDAL
intervenor. Also represented by THOMAS W. KRAUSE, AMY
J. NELSON, FARHEENA YASMEEN RASHEED, MICHAEL TYLER.
______________________
Before MOORE, Chief Judge, CLEVENGER and DYK, Circuit
Judges.
MOORE, Chief Judge.
Guardant Health, Inc. (Guardant) appeals a Patent
Trial and Appeal Board inter partes review final written
decision holding claims 1–11, 13, and 17–20 of U.S. Patent
No. 9,834,822 would have been obvious. We vacate and re-
mand.
BACKGROUND
DNA molecules comprise strands of units called nucle-
otides, which when repeated are called polynucleotides.
Cell free DNA (cfDNA), i.e., DNA present outside a cell, is
readily accessible for testing through extraction from bod-
ily fluids, such as blood. ’822 patent at 30:21–24, 35:62–67.
Guardant owns the ’822 patent, which is directed to sys-
tems and methods “for the detection of rare mutations and
copy number variations in” cfDNA. ’822 patent at Abstract.
One step in detecting mutations in cfDNA is converting
sample polynucleotides into “tagged parent polynucleo-
tides.” Id. at 18:19–22. Parent polynucleotides are tagged
by attaching “unique or non-unique identifiers, or molecu-
lar barcodes” to the parent strand. Id. at 38:4–6; see id. at
6:26–28, 15:20–27. The identifier or barcode is itself often
a polynucleotide sequence. Id. at 15:37–38, 32:61–63.
Claim 1 recites:
1. A method, comprising:
a) providing a population of cell free DNA
(“cfDNA”) molecules obtained from a bodily
sample from a subject;
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GUARDANT HEALTH, INC. v. VIDAL 3
b) converting the population of cfDNA mol-
ecules into a population of non-uniquely
tagged parent polynucleotides, wherein
each of the non-uniquely tagged parent pol-
ynucleotides comprises (i) a sequence from
a cfDNA molecule of the population of
cfDNA molecules, and (ii) an identifier se-
quence comprising one or more polynucleo-
tide barcodes;
c) amplifying the population of non-
uniquely tagged parent polynucleotides to
produce a corresponding population of am-
plified progeny polynucleotides;
d) sequencing the population of amplified
progeny polynucleotides to produce a set of
sequence reads;
e) mapping sequence reads of the set of se-
quence reads to one or more reference se-
quences from a human genome;
f) grouping the sequence reads into fami-
lies, each of the families comprising se-
quence reads comprising the same
identifier sequence and having the same
start and stop positions, whereby each of
the families comprises sequence reads am-
plified from the same tagged parent poly-
nucleotide;
g) at each genetic locus of a plurality of ge-
netic loci in the one or more reference se-
quences, collapsing sequence reads in each
family to yield a base call for each family at
the genetic locus; and
h) determining a frequency of one or more
bases called at the locus from among the
families.
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4 GUARDANT HEALTH, INC. v. VIDAL
Id. at claim 1 (emphases added).
Foundation Medicine, Inc. (FMI) petitioned for inter
partes review (IPR) of claims 1–13 and 17–20 of the ’822
patent, arguing the claims would have been obvious over a
combination including U.S. Patent No. 9,752,188 (Schmitt)
and the Fan article. 1 The Board instituted IPR and held
all petitioned claims, except claim 12, would have been ob-
vious. Found. Med., Inc. v. Guardant Health, Inc., No.
IPR2019-00652, 2020 WL 4873209, at *28 (P.T.A.B. Aug.
18, 2020) (FWD). Guardant appealed, and FMI thereafter
withdrew. The Director intervened to defend the Board’s
decision. We have jurisdiction under 28 U.S.C.
§ 1295(a)(4)(A).
DISCUSSION
I
Guardant argues the Board erroneously construed
“converting the population of cfDNA molecules into a pop-
ulation of non-uniquely tagged parent polynucleotides” to
mean “the number of different identifiers can be at least 2
and fewer than the number of polynucleotides in the sam-
ple.” See FWD, 2020 WL 4873209, at *11. The proper con-
struction of “non-uniquely tagged,” according to Guardant,
is the following “express definition” in the ’822 patent’s
written description: “the number of different identifiers can
be [] at least 2 and fewer than the number of polynucleo-
tides that map to the mappable base position.” ’822 patent
at 41:44–47 (emphasis added); see Appellant’s Opening Br.
at 26. The Director responds that the Board properly de-
termined the plain and ordinary meaning of non-uniquely
tagged means at least two but fewer than the number of
parent polynucleotides in the sample. Intervenor’s Br. at
1 Christina Fan et al., Noninvasive diagnosis of fe-
tal aneuploidy by shotgun sequencing DNA from maternal
blood, 105(42) PROC. NATL. ACAD. SCI. 16266–71 (2008).
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GUARDANT HEALTH, INC. v. VIDAL 5
26. The Director asserts the ’822 patent’s reference to “the
number of polynucleotides that map to the mappable base
position” is a single embodiment and that the “polynucleo-
tides that map to the mappable base position” refer to a
particular set of polynucleotides. Id. at 26–33 & n.7. We
agree with the Director.
Claim construction is a legal question that may be
based on underlying factual determinations. HTC Corp. v.
Cellular Commc’ns Equip., LLC, 877 F.3d 1361, 1367 (Fed.
Cir. 2017). We review the Board’s claim construction based
on the intrinsic record de novo and its factual findings for
substantial evidence. Id. Claim terms are generally given
their plain and ordinary meaning, i.e., the meaning the
terms would have to a person of ordinary skill in the art
when read in the context of the specification and prosecu-
tion history. Phillips v. AWH Corp., 415 F.3d 1303, 1312–
13 (Fed. Cir. 2005) (en banc). We depart from the plain and
ordinary meaning in only two instances: lexicography and
disavowal. GE Lighting Sols., LLC v. AgiLight, Inc., 750
F.3d 1304, 1309 (Fed. Cir. 2014). The bar for lexicography
is exacting. Thorner v. Sony Comput. Ent. Am. LLC, 669
F.3d 1362, 1365 (Fed. Cir. 2012). Lexicography applies
only where the patentee “clearly set[s] forth a definition of
the disputed claim term” and “clearly express[es] an in-
tent” to redefine the term. Id.The ’822 patent does not clearly set forth a definition of
non-uniquely tagged parent polynucleotides that displaces
the term’s plain and ordinary meaning. The passage
providing Guardant’s purported definition reads in full: “A
set of polynucleotides in the composition that map to a
mappable base position in a genome can be non-uniquely
tagged, that is, the number of different identifiers can be []
at least 2 and fewer than the number of polynucleotides that
map to the mappable base position.” ’822 patent at 41:41–
47 (emphases added). By its plain terms, this “definition”
merely explains non-uniquely tagging the particular sub-
set of the population of polynucleotides that map to a
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6 GUARDANT HEALTH, INC. v. VIDAL
mappable base position. Thus, even if the passage were
definitional, Guardant ignores that the definition applies
only to polynucleotides within the population that “map to
a mappable base position,” not the invention as a whole.
’822 patent at 41:41–47; see Appellant’s Opening Br. at 26.
This is consistent with the ’822 patent’s other disclosures.
Elsewhere, the ’822 patent does not describe the population
of polynucleotides as only those that map to a mappable
base position. The written description makes clear that
“[i]n some embodiments each polynucleotide in a set is map-
pable to a reference sequence.” 2 ’822 patent at 6:1–2 (em-
phasis added). It follows that other embodiments include
polynucleotides that do not map to a mappable base posi-
tion and thus are outside of the definition asserted by
Guardant.
Guardant also argues the Board’s construction encom-
passes prior art systems that the ’822 patent distinguishes.
Specifically, Guardant argues the patent distinguishes its
invention from prior art systems of “uniquely tag[ging]
every, or nearly every, different parent molecule in the
sample,” which “can be cumbersome and expensive.” ’822
patent at 41:1–2, 6. We do not agree. The portion of the
written description Guardant cites does not distinguish the
’822 patent’s invention from prior art systems—It never
mentions prior art systems and instead consistently refers
to the “methods disclosed herein.” See id. at 38:1–41:53.
Even if the ’822 patent was distinguishing prior art sys-
tems as “cumbersome and expensive,” such criticism is not
a clear “expression[] of manifest exclusion” of claim scope.
Epistar Corp. v. Int’l Trade Comm’n, 566 F.3d 1321, 1335
2 The parties agreed below, and do not dispute here,
that a mappable base position is “a position in the reference
sequence to which polynucleotide molecules can be confi-
dently mapped.” FWD, 2020 WL 4873209, at *7 n.6; see
Appellant’s Opening Br. at 10.
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GUARDANT HEALTH, INC. v. VIDAL 7
(Fed. Cir. 2009) (“A patentee’s discussion of the shortcom-
ings of certain techniques is not a disavowal of the use of
those techniques in a manner consistent with the claimed
invention.”); see Thorner, 669 F.3d at 1366 (“Mere criticism
of a particular embodiment . . . [alone] is not sufficient to
rise to the level of clear disavowal.”). We therefore hold
there is no error in the Board’s construction of non-
uniquely tagged parent polynucleotides.
II
Guardant next challenges the Board’s finding that
Schmitt teaches non-uniquely tagged parent polynucleo-
tides under the Board’s construction and its finding that a
skilled artisan would have had a reasonable expectation of
success in combining Schmitt’s hybrid Duplex Consensus
Sequencing (DCS) method with cfDNA. Guardant also ar-
gues the Board erroneously found a lack of nexus related
to objective indicia of nonobviousness. We hold substantial
evidence supports the Board’s finding that Schmitt teaches
non-uniquely tagged parent polynucleotides and its finding
regarding the reasonable expectation of success. We do,
however, vacate the Board’s obviousness determination
and remand for further fact finding because the Board’s ob-
jective indicia of nonobviousness analysis is not supported
by substantial evidence.
A. Schmitt
Guardant argues that, even under the Board’s con-
struction, the Board’s finding that Schmitt teaches non-
uniquely tagged parent polynucleotides is not supported by
substantial evidence. We review the Board’s legal determi-
nation of obviousness de novo and any underlying findings
of fact for substantial evidence. Outdry Techs. Corp. v.
Geox S.p.A., 859 F.3d 1364, 1367 (Fed. Cir. 2017). Substan-
tial evidence is “such relevant evidence as a reasonable
mind might accept as adequate to support a conclusion.”
FTC v. Ind. Fed’n of Dentists, 476 U.S. 447, 454 (1986) (ci-
tation omitted). What a prior art reference discloses is a
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8 GUARDANT HEALTH, INC. v. VIDAL
question of fact. In re Kahn, 441 F.3d 977, 985 (Fed. Cir.
2006).
The Board found Schmitt’s use of n-mer 3 tags in its hy-
brid DCS method teaches non-uniquely tagged parent pol-
ynucleotides. FWD, 2020 WL 4873209, at *13. Guardant
argues the Board incorrectly mapped Schmitt’s “n-mer
tags” onto claim 1’s “identifiers.” According to Guardant,
the identifiers disclosed in Schmitt are not the n-mer tags
standing alone, which are fewer than the millions of parent
polynucleotides, but are the n-mer tags plus the sheared
ends of endogenous DNA. The n-mer tags and sheared
ends together result in trillions of different identifiers that
exceed the number of parent polynucleotides and therefore,
according to Guardant, fall outside the scope of the Board’s
definition. See Appellant’s Opening Br. at 40–41. The Di-
rector responds that Guardant falsely conflates the identi-
fiers used to describe the non-unique barcodes (i.e., n-mer
tags) with the unique molecular identifiers (i.e., the n-mer
tags plus sheared DNA ends) and that the Board’s finding
is supported by substantial evidence. See Intervenor’s Br.
at 37–38. We agree with the Director.
Guardant’s argument confuses two different meanings
of identifier. The Board construed non-uniquely tagged to
mean that the “number of different identifiers (the tag
count) is . . . fewer than the number of parent polynucleo-
tides in the sample.” FWD, 2020 WL 4873209, at *10 (em-
phasis added). This is consistent with claim 1. Claim 1
describes the non-uniquely tagged parent polynucleotides
having two parts: (1) “a sequence from a cfDNA molecule”;
and (2) an “identifier sequence comprising one or more pol-
ynucleotide barcodes.” ’822 patent at claim 1 (emphasis
added). The Board’s findings regarding Schmitt map onto
3 An n-mer sequence is a tag where n is the number
of nucleotides. FWD, 2020 WL 4873209, at *11 n.11. A 4-
mer tag, for example, is a sequence of four nucleotides. Id.Case: 21-1104 Document: 42 Page: 9 Filed: 05/05/2023
GUARDANT HEALTH, INC. v. VIDAL 9
the claim language and the Board’s construction. Schmitt
discloses a “hybrid DCS method,” where sheared ends of
target polynucleotides are tagged with “a shorter n-mer
tag (such as 1 or 2 or 3 or 4 or more . . . bases).” Schmitt at
9:10–12. In finding Schmitt’s hybrid method teaches a pop-
ulation of non-uniquely tagged parent polynucleotides, the
Board found Schmitt’s 4-mer tag would produce 65,536
“unique identifiers,” i.e., the “tag count.” FWD, 2020 WL
4873209, at *12 (citing J.A. 1072 ¶ 127 & n.7 (Dr. Gabriel’s
declaration); J.A. 4459 ¶ 69 (Dr. Quackenbush’s declara-
tion)). When these unique identifiers are added to the
sheared ends (i.e., the claimed “sequence from a cfDNA
molecule of the population of cfDNA molecules”), they pro-
duce a “unique molecular identifier.” Schmitt at 9:9–14
(emphasis added). Because the 65,536 4-mer tag identifi-
ers are fewer than the millions of parent polynucleotides in
a sample, the hybrid method produces a population where
“more than one parent polynucleotide would necessarily
share the same short [4]-mer tag,” i.e., are non-uniquely
tagged. FWD, 2020 WL 4873209, at *13–16 (citing J.A.
1071–72 ¶¶ 126–27 (Dr. Gabriel’s declaration); J.A. 4459 ¶
69 (Dr. Quackenbush’s declaration)).
Schmitt’s disclosure is like the method disclosed in the
’822 patent, which explains that non-unique tags or bar-
codes are distinguishable and can be consistent with
uniquely identifying a particular molecule. In other words,
there may be non-unique barcodes that, when attached to
a particular molecule, may result in a unique identifier for
that molecule. Indeed, “barcodes are not necessarily
unique to one another in the plurality. In this example,
barcodes may be ligated to individual molecules such that
the combination of the bar code and the sequence it may be
ligated to creates a unique sequence that may be individu-
ally tracked.” ’822 patent at 39:13–18. The use of
“non[-]unique barcodes in combination with sequence data
of beginning (start) and end (stop) portions of sequence
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10 GUARDANT HEALTH, INC. v. VIDAL
reads may allow assignment of a unique identity to a par-
ticular molecule.” Id. at 39:19–22.
Moreover, Schmitt itself distinguishes non-uniquely
tagging from uniquely tagging. In addition to a 4-mer tag,
Schmitt discloses a method with a 12-mer tag, wherein
every target polynucleotide is labeled with “two distinct
SMI sequences,” Schmitt at 3:47–51, which results in more
tags than the number of polynucleotides in the sample, i.e.,
unique tagging. Schmitt at 6:59–64; see J.A. 1071 ¶ 126
(Dr. Gabriel’s declaration). In sum, while the combined
sheared end and 4-mer tag might result in a unique molec-
ular identifier, the population of parent polynucleotides is
non-uniquely tagged based on the claimed identifier.
Therefore, substantial evidence supports the Board’s find-
ing that Schmitt teaches non-uniquely tagged parent poly-
nucleotides.
B. Reasonable Expectation of Success
Guardant argues Schmitt’s method was “poorly suited
for cfDNA” and a skilled artisan therefore would not have
reasonably expected to successfully apply Schmitt’s
method to a population of cfDNA molecules. Appellant’s
Opening Br. at 42. It also argues the Board legally erred
in excluding some of Guardant’s evidence for being related
to tagging efficacy or efficiency, which is not claimed. Id.at 42–44; FWD, 2020 WL 4873209, at *26. The Director
responds that substantial evidence supports the Board’s
finding that there would be a reasonable expectation of suc-
cess in applying Schmitt’s method to cfDNA. Intervenor’s
Br. at 40–44. We agree with the Director.
Claim 1 of the ’822 patent claims the use of methods
applied to cfDNA. The Board addressed the use of Schmitt
with cfDNA, as recited in the Fan article, and relied on ev-
idence of Schmitt’s compatibility with the cfDNA sequenc-
ing platform used in Fan. FWD, 2020 WL 4873209, at *26.
Guardant does not directly challenge this finding. Instead,
it mounts a collateral attack arguing the Board should not
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GUARDANT HEALTH, INC. v. VIDAL 11
have rejected other evidence related to tagging efficiency
that would have led it to a different finding. As the Board
concluded, tagging efficiency, however, is not claimed. Cf.
Intelligent Bio-Sys., Inc. v. Illumina Cambridge Ltd., 821
F.3d 1359, 1367 (Fed. Cir. 2016) (“The reasonable expecta-
tion of success requirement refers to the likelihood of suc-
cess in combining references to meet the limitations of the
claimed invention.” (emphasis added)). We therefore hold
substantial evidence supports the Board’s finding that a
skilled artisan would have a reasonable expectation of suc-
cess in using Schmitt’s hybrid method to analyze cfDNA.
C. Objective Indicia of Nonobviousness
Guardant argues the Board erroneously found a lack of
evidence that its commercial embodiment, Guardant360, is
not coextensive with the claimed invention and therefore
was not entitled to a presumption of nexus. FWD, 2020 WL
4873209, at *26–27. The Board’s conclusion rested on its
finding that Guardant did not cite Dr. Quackenbush’s dec-
laration in its briefing and its refusal “to search through
Dr. Quackenbush’s [d]eclarations for this evidence.” Id.(citing DeSilva v. DiLeonardi, 181 F.3d 865, 866–67 (7th
Cir. 1999) (“A brief must make all arguments accessible to
the judges, rather than ask them to play archeologist with
the record.”)). Whether a presumption of nexus applies is
a question of fact. Fox Factory, Inc. v. SRAM, LLC, 944
F.3d 1366, 1373 (Fed. Cir. 2019).
The Board’s finding that Guardant360 is not coexten-
sive with claim 1 of the ’822 patent, and therefore its nexus
and overall obviousness determinations, is not supported
by substantial evidence. The Board’s finding was falsely
premised on Guardant’s failure to cite evidence, such as ex-
pert testimony, establishing nexus. Contrary to the
Board’s reasoning, Guardant’s response brief expressly re-
lied on Dr. Quackenbush’s opinion that Guardant360 em-
bodies claim 1 to support its argument of a presumption of
nexus. J.A. 640–41 (citing J.A. 4489–97 ¶¶ 156–66). On
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12 GUARDANT HEALTH, INC. v. VIDAL
those same pages, Guardant mapped Guardant360 to
claim 1 while again referencing Dr. Quackenbush’s testi-
mony. J.A. 641. The Board simply overlooked Guardant’s
clear reliance on this evidence. Because the Board’s find-
ing that there was inadequate evidence to show that Guar-
dant360 is coextensive with claim 1 was based on a clearly
mistaken view of the evidence, we vacate the Board’s obvi-
ousness determination and remand for further fact find-
ing. 4
The Board also erred as a matter of law in its treatment
of the articles that both Guardant and Dr. Quackenbush
relied on for mapping Guardant360 to claim 1. The Board
reasoned the articles were insufficient because the articles
themselves, as opposed to testimony interpreting those ar-
ticles, “do not provide any legal or factual analysis.” FWD,
2020 WL 4873209, at *27. This was premised on the
Board’s erroneous view that there was no expert testimony
mapping claim 1 onto Guardant360. Id. In other words,
the Board required Guardant’s articles to establish nexus
without expert testimony linking the articles’ discussion of
Guardant360 to claim 1 of the ’822 patent. See id. This
was error. Expert testimony is necessary in many cases.
See Perfect Web Techs., Inc. v. InfoUSA, Inc., 587 F.3d 1324,
1330 (Fed. Cir. 2009) (“If the relevant technology were com-
plex, the court might require expert opinions.”); cf. id. (“No
expert opinion is required to appreciate the potential value
4 The Director argues Guardant improperly incorpo-
rated arguments from Dr. Quackenbush’s declaration in vi-
olation of 37 C.F.R. § 42.6(a)(3) (“Arguments must not be
incorporated by reference from one document into another
document.”). Intervenor’s Br. at 45–46. This argument is
inapt because Guardant’s response brief maps claim 1’s el-
ements to Guardant360 by relying on the evidence and ex-
pert declaration, not by incorporating legal arguments.
J.A. 640–41.
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GUARDANT HEALTH, INC. v. VIDAL 13
to persons of such skill in this art” where “ordinary skill in
the relevant art required only a high school education and
limited marketing and computer experience.”). Here, a
person of ordinary skill in the art had “a doctorate degree
(Ph.D.) in genetics, molecular biology, bioinformatics, or a
related field, and at least five years of research in an aca-
demic or industry setting, including at least two to three
years of research experience in the field of cancer ge-
nomics.” FWD, 2020 WL 4873209, at *6. Guardant’s reli-
ance on Dr. Quackenbush’s testimony interpreting the
cited articles and mapping Guardant360 to claim 1 is ap-
propriate in this instance. The Board erred as a matter of
law in disregarding Guardant’s evidence to establish a pre-
sumption of nexus. On remand, the Board must consider
the articles in light of the parties’ arguments and all other
appropriate evidence.
CONCLUSION
We have considered the parties’ remaining arguments
and find them unpersuasive. For the reasons given, we va-
cate the Board’s obviousness determination and remand
for further fact finding consistent with this opinion.
VACATED AND REMANDED
COSTS
Costs awarded to Guardant.