Laboratory Corporation of America Holdings v. Ravgen, Inc.

N OTE: This disposition is nonprecedential.
United States Court of Appeals
for the Federal Circuit
______________________
LABORATORY CORPORATION OF AMERICA
HOLDINGS,
Appellant
v.
RAVGEN, INC.,
Appellee
______________________
2023-1517
______________________
Appeal from the United States Patent and Trademark
Office, Patent Trial and Appeal Board in No. IPR2021-
01026.
______________________
Decided: January 29, 2025
______________________
G REGORY A. CASTANIAS , Jones Day, Washington, DC,
argued for appellant. Also represented by AMELIA A.
D EG ORY , BRENDAN D. D UFFY , T RACY A. STITT , J ENNIFER L.
SWIZE; G ASPER L AROSA, New York, NY; J OHN C. ALEMANNI,
Kilpatrick Townsend & Stockton LLP, Raleigh, NC;
CYNTHIA B. ROTHSCHILD, I, Winston-Salem, NC.
BRIAN MATTY , Desmarais LLP, New York, NY, argued
for appellee. Also represented by J OHN M. D ESMARAIS ,
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LABORATORY CORPORATION OF AMERICA HOLDINGS v.
RAVGEN, INC.
2
K ERRI-A NN L IMBEEK; G ABRIELLE E. HIGGINS , San Fran-
cisco, CA.
______________________
Before L OURIE, BRYSON, and STARK, Circuit Judges.
L OURIE, Circuit Judge.
Laboratory Corporation of America Holdings (“Lab-
corp”) appeals from the final written decision of the U.S.
Patent Trial and Appeal Board (“the Board”) holding that
claims 1–9 and 21–30 of U.S. Patent 7,727,720 (“the ’720
patent”) had not been shown to be unpatentable. Lab’y
Corp. of Am. Holdings v. Ravgen, Inc., No. IPR2021-01026,
2022 WL 17583185 (P.T.A.B. Dec. 12, 2022) (“Decision”).
For the following reasons, we affirm.
BACKGROUND
The instant case is a companion to Laboratory Corpo-
ration of America Holdings v. Ravgen, Inc., No. 2023-1342,
2025 WL 32904 (Fed. Cir. Jan. 6, 2025) (“Labcorp”) ad-
dressing related U.S. Patent 7,332,277 and decided by this
court on January 6, 2025. In that case, we affirmed the
Board’s upholding of similar claims against overlapping
prior art. Ravgen, Inc. (“Ravgen”) owns the ’720 patent,
which is directed to a “rapid, non-invasive method for de-
termining the sequence of DNA from a fetus” that can be
used “for detection of chromosomal abnormalities.” ’720
patent, col. 1, ll. 23–27. The ’720 patent describes a method
of adding an agent that impedes cell lysis to a maternal
blood sample to increase the percentage of cell-free fetal
DNA relative to the cell-free maternal DNA in the sample.
Id. at col. 210, ll. 19–24; id. at col. 89, ll. 35–37. The speci-
fication lists various agents as membrane stabilizers,
cross-linkers, and cell lysis inhibitors, including formalde-
hyde and glucose. Id. at col. 32, l. 65–col. 33, l. 28.
Claim 1 is representative for the issues on appeal and
reads as follows:
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1. A method for detecting a free nucleic acid,
wherein said method comprises: (a) isolating free
nucleic acid from a non-cellular fraction of a sam-
ple, wherein said sample comprises an agent that
impedes cell lysis, if cells are present, and wherein
said agent is selected from the group consisting of
membrane stabilizer, cross-linker, and cell lysis in-
hibitor; and (b) detecting the presence or absence of
the free nucleic acid.
Id. at col. 535, ll. 15–21 (emphasis added).
In its petition for inter partes review, Labcorp asserted
three grounds of unpatentability with Lee1 as the primary
reference, and a fourth ground with Sorenson2 as the pri-
mary reference. For the Lee-based grounds, Labcorp as-
serted that all challenged claims would have been
anticipated or rendered obvious by Lee alone or in combi-
nation with Sorenson. For the Sorenson-based ground,
Labcorp asserted that all challenged claims would have
been rendered obvious by Sorenson in combination with
Rao.3
Lee reports a study on quantitating cell-free genomic
DNA in serum and in plasma. J.A. 3017. Lee discusses a
protocol that collected blood samples in tubes with either
acid citrate dextrose (“ACD”), ethylenediaminetetraacetic
1 Tzong-Hae Lee et al., Quantitation of Genomic
DNA in Plasma and Serum Samples: Higher Concentra-
tions of Genomic DNA Found in Serum than in Plasma, 41
T RANSFUSION 276 (2001), J.A. 3017–23.
2 George D. Sorenson et al., Soluble Normal and Mu-
tated DNA Sequences from Single-Copy Genes in Human
Blood, 3 CANCER EPIDEMIOLOGY , B IOMARKERS &
P REVENTION 67 (1994), J.A. 3024–29.
3 International Patent Application Publication WO
2003/018757.
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acid (“EDTA”), or no anticoagulant. J.A. 3018. The sam-
ples were processed, and DNA was quantitated using a
PCR assay daily for up to seven days. Id. It is undisputed
that ACD includes dextrose and that dextrose is a form of
glucose. Decision, at *8. Sorenson reports a study on ex-
tracellular DNA in cancer patients. J.A. 3024. The study
identified increased quantities of extracellular DNA and
mutated sequences in patients with pancreatic cancer. Id.
Sorenson reports that “cellular DNA can be released dur-
ing clotting of whole blood.” Id. And Rao discloses a
method of stabilizing rare cancer cells in a blood sample
using paraformaldehyde. Rao at Abstract; see id. at p. 3, ll.
12–19.
The Board concluded that the challenged claims had
not been shown to be unpatentable. First, in interpreting
the claim, the Board explained that the plain language of
claim 1 requires that, “if cells are present,” the claimed
agent “impedes cell lysis.” Decision, at *9. Based on that
understanding, the Board determined that, to establish an-
ticipation by Lee, Labcorp needed to show that the dextrose
present in Lee’s blood samples, by way of the addition of
ACD, actually impeded cell lysis. Id. The Board noted that
Labcorp could satisfy its burden if it could show that the
dextrose in Lee “even minimally impeded cell lysis” be-
cause the claims “do not require any particular degree of
lysis impedance.” Id. at *14. But after reviewing the dis-
closures of Lee and the testimony of the parties’ competing
experts, the Board found that “the preponderance of the ev-
idence does not support that the dextrose in Lee impeded
cell lysis.” Id. at *15. Accordingly, the Board determined
that the challenged claims had not been shown to be antic-
ipated by Lee. Id. The Board determined that the Lee-
based obviousness grounds failed for the same reason. Id.
With respect to the Sorenson-based ground, the Board
concluded that Labcorp failed to show that a person of or-
dinary skill in the art “would have been motivated to add
formaldehyde to Sorenson’s method of detecting cell-free
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DNA in plasma.” Id. at *16. The “key question” the Board
addressed in its analysis was whether a person of ordinary
skill in the art “would have been concerned with formalde-
hyde’s potential effects on DNA, and cell-free fetal DNA in
particular.” Id. at *17. The Board found that “formalde-
hyde was known to have detrimental effects on nucleic ac-
ids” and that a person of ordinary skill in the art would not
have known how to “tailor the use of formaldehyde to ame-
liorate” those expected detrimental effects. Id. at *20. The
Board therefore determined that Labcorp had not shown
that a person of ordinary skill would have been motivated
to combine Sorenson and Rao in the manner proposed. Id.
Labcorp timely appealed, and we have jurisdiction un-
der 28 U.S.C. § 1295(a)(4)(A).
D ISCUSSION
Labcorp’s primary argument on appeal is that the
Board engaged in improper implicit or post hoc claim con-
struction of the term “agent that impedes cell lysis” and
that, under the proper construction of the “agent” term, Lee
anticipates the claims. According to Labcorp, all that the
claims require is for dextrose to be present in the sample
because it was known to impede cell lysis. Alternatively,
Labcorp argues that even under the erroneous construc-
tion, the Board findings on the Lee-based grounds were not
supported by substantial evidence. Labcorp also argues
that the Board legally erred in considering the motivation
to combine Sorenson and Rao and that, in any event, the
Board’s findings on that issue were not supported by sub-
stantial evidence. We address each argument in turn.
I
Claim construction is a question of law reviewed de
novo. Intel Corp. v. Qualcomm Inc., 21 F.4th 801, 808 (Fed.
Cir. 2021). The words of a claim are generally given their
ordinary and customary meaning as understood by a per-
son of ordinary skill in the relevant art at the time of the
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invention. Phillips v. AWH Corp., 415 F.3d 1303, 1312–13
(Fed. Cir. 2005) (en banc).
The Board expressly construed the claim term “agent
that impedes cell lysis” to “exclude chelators used as anti-
coagulants.” Decision, at *6. Neither party challenges that
express construction. The Board, in analyzing Lee, then
explained that “[b]y its plain language, claim 1 requires
that ‘if cells are present,’ as they are in Lee’s samples, the
claimed agent ‘impedes cell lysis.’” Id. at *9. Labcorp ar-
gues that the Board’s understanding of the plain language
of the claims amounts to an improper implicit or post hoc
construction because the claims do not require the agent to
actually impede cell lysis. According to Labcorp, the
“agent” term “could not be simpler” and requires nothing
more than “an agent selected from one of the three enumer-
ated categories (membrane stabilizers, cross-linkers, and
cell-lysis inhibitor[s]).” Labcorp Br. 30. We disagree with
Labcorp.
There is no ambiguity in the claim language; “if cells
are present,” the claimed agent is required to “impede[] cell
lysis.” ’720 patent, col. 535, ll. 15–21. That understanding
is confirmed by the structure of the claims. Claim 1, from
which all challenged claims depend, contains two wherein
clauses describing the agent; the first requires “an agent
that impedes cell lysis, if cells are present,” and the second
requires the agent to be “selected from the group consisting
of membrane stabilizer, cross-linker, and cell lysis inhibi-
tor.” Id. Labcorp’s proposed construction would essentially
read the first clause out of the claim, as its construction
requires only that the agent be “selected from” one of the
three enumerated categories. See Labcorp Br. 30–33; see
also id. at 35 (“The claimed ‘agent’ need be nothing more
than one that is known to impede cell lysis.”). Claims, how-
ever, should be interpreted to give effect to all their terms.
Bicon, Inc. v. Straumann Co., 441 F.3d 945, 950 (Fed. Cir.
2006). As such, the plain language of the claims requires
both that the agent “impedes cell lysis, if cells are present”
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and that the agent is selected from the enumerated group.
The specification further confirms that understanding of
the claims, i.e., that the agent must actually impede cell
lysis. See, e.g., ’720 patent, col. 6, ll. 49–50 (explaining that
a stabilizing agent “may be added to the maternal blood
sample to reduce maternal cell lysis” (emphasis added)).
The Board properly determined that the plain lan-
guage of the claims required Labcorp to show that “dex-
trose in Lee’s samples ‘impedes cell lysis’ ‘if cells are
present.’” Decision, at *9. The Board even agreed with
Labcorp that “the challenged claims do not require any par-
ticular degree of lysis impedance,” Decision, at *14; see also
Labcorp Br. 32–33, and that “even minimally imped[ing]
cell lysis” is all the claims required, Decision, at *14. Lab-
corp’s proposed construction, however, would allow any
agent that is merely capable of impeding cell lysis to satisfy
the claims. But, as discussed above, the plain language of
the claims requires not just an agent capable of impeding
cell lysis, but one “that impedes cell lysis.” We therefore
see no error in the Board’s understanding of the claims
through implicit claim construction, post hoc claim con-
struction, or otherwise.
II
We next address Labcorp’s arguments with respect to
the Lee-based grounds. The only dispute between the par-
ties is whether Lee discloses the “agent” limitation. Ac-
cording to Labcorp, the Board failed to evaluate Lee from
the perspective of a person of skill in the art, and its finding
that Lee did not disclose or suggest that the dextrose (in
ACD) added to the blood sample impeded cell lysis was not
supported by substantial evidence. Labcorp Br. 38–44. We
disagree.
Anticipation is a question of fact reviewed for substan-
tial evidence. Genentech, Inc. v. Hospira, Inc., 946 F.3d
1333, 1337 (Fed. Cir. 2020). Obviousness is a question of
law based on underlying findings of fact. KSR Int’l Co. v.
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Teleflex Inc., 550 U.S. 398, 427 (2007). We review the
Board’s legal conclusion on obviousness de novo and its un-
derlying findings of fact for substantial evidence. HTC
Corp. v. Cellular Commc’ns Equip., LLC, 877 F.3d 1361,
1369 (Fed. Cir. 2017). What a reference teaches and the
presence or absence of a motivation to combine references
are questions of fact. PAR Pharm., Inc. v. TWI Pharms.,
Inc., 773 F.3d 1186, 1196–97 (Fed. Cir. 2014).
Contrary to Labcorp’s assertions, the Board carefully
considered Lee from the perspective of a person of skill in
the art. Indeed, the Board considered each of the three
mechanisms through which Labcorp alleged a person of or-
dinary skill in the art would have understood the dextrose
in Lee to actually impede cell lysis. Decision, at *10–11. It
did so by considering the disclosures of Lee, the testimony
of both experts, and the specific circumstances present in
Lee. See, e.g., id. at *10 (noting that Dr. Edwards’ testi-
mony that carbohydrates, like dextrose, were known to
have a role in membrane stabilization was “consistent with
the teaching in the ’720 patent”); id. (noting that “failure to
maintain isotonicity does not necessarily cause cell lysis”);
id. at *11 (finding that dextrose’s ability to prevent cell ly-
sis by providing a nutrient source was reduced by Lee’s
storage temperature). Based on that evidence, the Board
reasonably concluded that “any effect that [dextrose]
has . . . to improve the health and stability of cells is not
realized in any of the Lee experiments.” Id.
Labcorp’s disagreement with the Board’s conclusions
after weighing the evidence does not demonstrate a failure
to consider Lee from the perspective a person of skill in the
art. Eli Lilly & Co. v. Teva Pharms. Int’l GmbH, 8 F.4th
1331, 1347 (Fed. Cir. 2021) (“[D]isagreement with the
Board’s interpretations of [a reference] does not amount to
a demonstration that the Board somehow failed to use the
proper analysis.”). We do not reweigh evidence on appeal.
In re NTP, Inc., 654 F.3d 1279, 1292 (Fed. Cir. 2011); Re-
gents of Univ. of Cal. v. Broad Inst., Inc., 903 F.3d 1286,
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1294 (Fed. Cir. 2018) (“It is not our role to ask whether sub-
stantial evidence supports fact-findings not made by the
Board, but instead whether such evidence supports the
findings that were in fact made.”). Here, we conclude that
the Board’s finding that Lee does not disclose the claimed
agent that “impedes cell lysis” was supported by substan-
tial evidence.
As the Board noted, “[n]owhere does Lee hint at the
significance of dextrose in the samples or attribute any dif-
ference in the observed differences in DNA levels to any
specific cause beyond clotting.” Decision, at *14. Thus,
Labcorp’s evidence that the “dextrose in Lee impedes cell
lysis rest[ed] primarily on the testimony of Dr. Edwards.”
Id. The Board considered that evidence but concluded that
it was “circumstance specific” and that Labcorp had failed
to persuasively address “the ability of dextrose to impede
cell lysis under the conditions present in Lee.” Id. Simi-
larly, the Board’s finding that the difference in cell-free
DNA levels seen in serum compared to plasma was not
shown to be attributable to dextrose was supported by sub-
stantial evidence. See id. at *12–14 (evaluating Lee Figure
4 and the associated expert testimony). The Board’s con-
clusion that the Lee-based grounds did not render the chal-
lenged claims unpatentable was therefore supported by
substantial evidence.
III
Finally, we turn to Labcorp’s argument that the
Board’s analysis of the motivation to combine Sorenson and
Rao was both legally flawed and not supported by substan-
tial evidence. Labcorp largely repeats the arguments made
against a motivation to combine in the companion case.
Compare Labcorp Br. 48 (“[T]he Board here erroneously
read various atextual limitations into the claims— . . . that
the free-floating DNA not be damaged[.]”), and id. at 52
(“[T]he Board committed legal error in requiring a height-
ened and untenable standard for proving a motivation to
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combine[.]”), and id. at 58 (“The Board likewise failed to
consider Rao for everything it teaches.”), with Labcorp,
2025 WL 32904, at *4 (“According to Labcorp, the Board
read into the claims additional limitations prohibiting
DNA damage[.]”), and id. at *2 (“Labcorp’s first argu-
ment—that the Board imposed an improperly heightened
standard for obviousness . . . .”), and id. at *4 (“Labcorp ar-
gues that the Board ignored Rao’s teaching . . . .”). In fact,
the same reference—Rao—was relied upon for its formal-
dehyde teachings in both cases. And as the Board noted,
the “key question” in both cases was “whether a [person of
ordinary skill in the art] would have been concerned with
formaldehyde’s potential effects on DNA, and cell-free fetal
DNA in particular.” Decision, at *17, see Labcorp, 2025 WL
32904, at *4. In both cases, the Board relied on similar
reasoning to answer that question in the affirmative and
find no motivation to combine the primary reference with
Rao. See Decision, at *17; Labcorp, 2025 WL 32904, at *2.
For reasons similar to those discussed in the companion
case, we find that the Board’s decision with respect to mo-
tivation to combine was not legally erroneous and was sup-
ported by substantial evidence. See Labcorp, 2025 WL
32904, at *2–5.
CONCLUSION
We have considered Labcorp’s remaining arguments
but find them unpersuasive. For the foregoing reasons, we
affirm the Board’s decision in IPR2021-01026, holding
claims 1–9 and 21–30 of the ’720 patent not shown to be
unpatentable.
AFFIRMED
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