Enzo Biochem Inc. v. Applera Corp.

NOTE: This disposition is nonprecedential.
United States Court of Appeals
for the Federal Circuit
______________________
ENZO BIOCHEM INC, ENZO LIFE SCIENCES, INC,
YALE UNIVERSITY,
Plaintiffs-Appellants
v.
APPLERA CORP., TROPIX INC,
Defendants-Appellees
______________________
2016-1881
______________________
Appeal from the United States District Court for the
District of Connecticut in No. 3:04-cv-00929-JBA, Judge
Janet Bond Arterton.
______________________
Decided: August 2, 2017
______________________
L. GENE SPEARS, Baker Botts, LLP, Houston, TX, ar-
gued for plaintiffs-appellants. Also represented by
MICHAEL HAWES.
ROBERT N. HOCHMAN, Sidley Austin LLP, Chicago, IL,
argued for defendants-appellees. Also represented by
CARTER GLASGOW PHILLIPS, JENNIFER J. CLARK, Washing-
ton, DC; NICHOLAS P. GROOMBRIDGE, JENNIFER H. WU,
2 ENZO BIOCHEM INC. v. APPLERA CORP.
ERIC ALAN STONE, Paul, Weiss, Rifkind, Wharton &
Garrison LLP, New York, NY.
______________________
Before PROST, Chief Judge, O’MALLEY, and WALLACH,
Circuit Judges.
O’MALLEY, Circuit Judge.
Enzo Biochem, Inc., Enzo Life Sciences, Inc., and Yale
University (collectively, “Enzo”) appeal from the District
of Connecticut’s entry of summary judgment in favor of
Applera Corp. and Tropix, Inc. (collectively, “Applera”).
See Enzo Biochem, Inc. v. Applera Corp. (District Court
Decision), No. 3:04cv929 (JBA), 2016 U.S. Dist. LEXIS
20904 (D. Conn. Feb. 22, 2016). Because the district court
accurately interpreted this court’s decision regarding the
proper construction of the claims in U.S. Patent No.
5,449,767 (“the ’767 patent”) and correctly analyzed
Enzo’s doctrine of equivalents argument, we affirm.
I. BACKGROUND
With this appeal, this court now has considered this
infringement action on three separate occasions over the
course of thirteen years of litigation between these par-
ties. We assume the parties are familiar with the back-
ground facts, and we therefore recite only those facts
relevant to our decision in this appeal.
A. DNA and RNA Sequencing and the ’767 Patent
As explained in the previous appeals, DNA and RNA
are composed of a series of units called “nucleotides.”
Enzo Biochem, Inc. v. Applera Corp. (Enzo II), 780 F.3d
1149, 1150 (Fed. Cir. 2015) (quoting Enzo Biochem, Inc. v.
Applera Corp. (Enzo I), 599 F.3d 1325, 1328 (Fed. Cir.
2010)). Each nucleotide is composed of a nitrogenous
base, a pentose sugar, and a phosphate group. Id. at
1150–51 (quoting Enzo I, 599 F.3d at 1328). Two strands
of DNA or RNA having complementary nitrogenous bases
ENZO BIOCHEM INC. v. APPLERA CORP. 3
will “hybridize” to form a double-stranded complex. Id. at
1151 (quoting Enzo I, 599 F.3d at 1328).
The technology at issue in this case deals with the use
of nucleotide probes to detect the presence of a particular
DNA or RNA sequence in a sample or to identify an
otherwise unknown DNA sequence. In our previous
opinions, we explained how hybridization can be used to
detect the presence of a nucleic acid:
Because hybridization occurs in a predictable
manner between complementary strands, it is
possible to detect the presence of a nucleic acid of
interest in a sample. For example, a chemical en-
tity, called a “label,” can be attached to or incorpo-
rated into a nucleic acid strand of a known
sequence, called a “probe,” which will hybridize
with a complementary sequence of interest, called
a “target.” Once the probe is hybridized with the
target, a detectable signal is generated either
from the label itself (referred to as “direct detec-
tion”) or from a secondary chemical agent that is
bound to the label (referred to as “indirect detec-
tion”). If a signal is detected from the sample af-
ter all unhybridized probes have been removed,
detection of the signal implies the presence of a
target in that sample.
Id. (quoting Enzo I, 599 F.3d at 1328).
The ’767 patent explains that “[m]any procedures em-
ployed in biomedical research and recombinant DNA
technology rely heavily on the use of” radioactive labels,
such as isotopes of hydrogen, phosphorus, carbon, or
iodine. ’767 patent, col. 1 ll. 23–27. When used as labels,
these radioactive compounds provide “useful indicator
probes that permit the user to detect, monitor, localize, or
isolate nucleic acids and other molecules of scientific or
clinical interest, even when present in only extremely
small amounts.” Id. at col. 1 ll. 27–32. But the ’767
4 ENZO BIOCHEM INC. v. APPLERA CORP.
patent notes that the use of these radioactive materials
has “serious limitations and drawbacks.” Id. at col. 1 ll.
35–37. For example, elaborate safety precautions are
necessary for the preparation, utilization, and disposal of
the isotopes to avoid potentially hazardous levels of
exposure to the radioactive material. Id. at col. 1 ll. 27–
41. The radioactive material also is expensive to use and
purchase. Id. at col. 1 ll. 41–46. And it is often unstable,
with a short shelf-life. Id. at col. 1 ll. 46–52.
As an alternative to the use of radioactive labels, the
’767 patent explains that “a series of novel nucleotide
derivatives that contain biotin, iminobiotin, lipoic acid,
and other determinants attached covalently to the pyrim-
idine or purine ring have been synthesized.” Id. at col. 2
ll. 63–68. These nucleotide derivatives interact “specifi-
cally and uniquely with proteins such as avidin or anti-
bodies.” Id. at col. 3 ll. 2–3. “If avidin is coupled to
potentially demonstrable indicator molecules, including
fluorescent dyes, . . . electron-dense reagents, . . . or
enzymes capable of depositing insoluble reaction prod-
ucts, . . . the presence, location, or quantity of a biotin
probe can be established.” Id. at col. 1 ll. 61–67.
The ’767 patent asserts that the use of this modified
detection approach provides “detection capacities equal to
or greater than procedures which utilize radioisotopes and
[it] often can be performed more rapidly and with greater
resolving power.” Id. at col. 3 ll. 9–13. The ’767 patent
further describes these new nucleotide derivatives as
providing an approach to detection that is “relatively
inexpensive[],” does not require “elaborate safety proce-
dures,” uses “chemically stable” derivatives, and allows
for “the development of safer, more economical, more
rapid, and more reproducible research and diagnostic
procedures.” Id. at col. 3 ll. 14–28.
ENZO BIOCHEM INC. v. APPLERA CORP. 5
Claim 1 of the ’767 patent covers an oligo- or polynu-
cleotide containing a nucleotide having the following
structure:
See id. at col. 30 l. 48–col. 31 l. 21. The disputed language
of claim 1 involves the following limitation: “wherein A
comprises at least three carbon atoms and represents at
least one component of a signaling moiety capable of
producing a detectable signal . . . .” Id. at col. 30 ll. 66–68.
All other asserted claims of the ’767 patent depend,
directly or indirectly, from claim 1. Claim 8 depends from
claim 1 and claims, “[a]n oligo- or polynucleotide of claim
1 wherein the linkage group includes the moiety –CH2–
NH–.” Id. at col. 31 ll. 36–37. Claim 67 depends from
claim 1 and claims, “[a]n oligo- or polynucleotide of claim
1 or 48 wherein A comprises an indicator molecule.” Id.
at col. 36 ll. 42–43. Claim 68 depends from claim 67 and
claims, “[a]n oligo- or polynucleotide of claim 67 wherein
said indicator molecule is fluorescent, electron dense, or is
an enzyme capable of depositing insoluble reaction prod-
ucts.” Id. at col. 36 ll. 44–47. Claim 70 depends from
claim 68 and claims, “[a]n oligo- or polynucleotide of claim
68 wherein the fluorescent indicator molecule is selected
from the group consisting of fluorescein and rhodamine.”
Id. at col. 36 ll. 51–53.
B. Procedural History
This litigation began in 2004, when Enzo filed suit
against Applera alleging infringement of six patents,
including the ’767 patent, that generally cover various
techniques and processes for detecting the presence of a
particular strand of DNA or RNA in a sample. In 2006,
the district court construed the claims of all six patents.
6 ENZO BIOCHEM INC. v. APPLERA CORP.
After multiple years of litigation and an appeal to this
court regarding invalidity issues decided on summary
judgment, see Enzo I, 599 F.3d at 1332–43, Enzo and
Applera went to trial in October 2012. Enzo limited its
infringement contentions during the jury trial to claims 1,
8, 67, 68, and 70 of the ’767 patent. The jury found Ap-
plera infringed the claims at issue and awarded $48.6
million in damages.
After the district court entered final judgment, Ap-
plera appealed. Applera argued that the district court
erred in its claim construction because the claims of the
’767 patent only cover indirect detection. In the alterna-
tive, Applera argued that, if the claims cover direct detec-
tion, they are invalid for lack of written description and
lack of enablement. We agreed with Applera and re-
versed the district court’s claim construction because we
concluded that “the inventors were claiming only indirect
detection.” Enzo II, 780 F.3d at 1156. Given that conclu-
sion, we held that “[t]he district court erred in construing
the disputed claims of the patent-in-suit to cover both
direct and indirect detection.” Id. at 1157. We treated
claim 1 as representative, id. at 1152, and specifically
stated that “claim 1 is limited to indirect detection,” id. at
1157. We then remanded the case to the district court to
determine whether the accused product infringes under
the proper claim construction. Id.
On remand, Enzo moved for entry of judgment on the
jury verdict, and Applera moved for summary judgment of
noninfringement. District Court Decision, 2016 U.S. Dist.
LEXIS 20904, at *3. The district court agreed with Ap-
plera that our decision in Enzo II covered all claims of the
’767 patent, not just claim 1 as argued by Enzo, and
rejected Enzo’s doctrine of equivalents argument relating
to claims 1 and 8. Id. at *13–14, 20–22. The district court
therefore denied Enzo’s motion for judgment on the jury
verdict and granted Applera’s motion for summary judg-
ment. Id. at *22–23. Enzo appealed. We possess subject
ENZO BIOCHEM INC. v. APPLERA CORP. 7
matter jurisdiction pursuant to 28 U.S.C. § 1295(a)
(2012).
II. DISCUSSION
We review a district court’s grant of summary judg-
ment under the law of the regional circuit. Teva Pharm.
Indus. Ltd. v. AstraZeneca Pharm. LP, 661 F.3d 1378,
1381 (Fed. Cir. 2011). The Second Circuit reviews the
grant of summary judgment de novo. Major League
Baseball Props., Inc. v. Salvino, Inc., 542 F.3d 290, 309
(2d Cir. 2008). Summary judgment is proper when,
drawing all justifiable inferences in the non-movant’s
favor, “there is no genuine dispute as to any material fact
and the movant is entitled to judgment as a matter of
law.” Fed. R. Civ. P. 56(a); see also Anderson v. Liberty
Lobby, Inc., 477 U.S. 242 (1986).
In addressing the parties’ arguments, we first address
the scope of Enzo II and its effect on claims 67, 68, and 70.
We then consider Enzo’s doctrine of equivalents argument
regarding claims 1 and 8. 1
A. The Scope of Enzo II
Enzo argues that the district court incorrectly inter-
preted our decision in Enzo II. Enzo asserts that Enzo II
only dealt with claim 1 and left intact the previously-
construed scope of claims 67, 68, and 70, covering both
direct and indirect detection. Based on its view of our
decision in Enzo II, Enzo contends that we should reverse
the current judgment on claims 67, 68, and 70, and rein-
state the jury’s finding of infringement and damages
award.
1 Enzo does not contest that claims 1 and 8 are not
literally infringed under our claim construction in Enzo
II. See District Court Decision, 2016 U.S. Dist. LEXIS
20904, at *15.
8 ENZO BIOCHEM INC. v. APPLERA CORP.
We conclude that, after carefully parsing our decision,
the district court correctly interpreted Enzo II. As the
district court explained, Enzo II consistently refers to the
“claims” at issue in that appeal, which extended beyond
claim 1 to include claims 8, 67, 68, and 70. See District
Court Decision, 2016 U.S. Dist. LEXIS 20904, at *14. For
example, our opinion in Enzo II, after acknowledging that
Enzo had asserted claims 1, 8, 67, 68, and 70, states that
the district court “erred in its claim construction by find-
ing that the claims at issue covered direct detection.”
Enzo II, 780 F.3d at 1150 (emphasis added). We reiterat-
ed this statement in the conclusion, where we stated,
“[t]he district court erred in construing the disputed
claims of the patent-in-suit to cover both direct and
indirect detection.” Id. at 1157 (emphasis added). The
opinion also looks to the specification to consider whether
it includes any teaching of direct detection applicable to
the claims and concludes that the specification does not
“support[] the inclusion of direct detection.” Id. at 1156.
As noted by the district court, it would have been illogical
for us to recognize the existence of five claims in the
appeal and then repeatedly refer to the “claims at issue”
or the “disputed claims” when referring only to claim 1
and not to claims 67, 68, and 70. See District Court
Decision, 2016 U.S. Dist. LEXIS 20904, at *14.
The district court also correctly noted that our deci-
sion in Enzo II acknowledged Applera’s alternative inva-
lidity arguments regarding lack of written description and
lack of enablement, but did not address the merits of
those arguments. Id. We did not need to address Ap-
plera’s alternative arguments because our analysis found
that the scope of the claims at issue, including claims 67,
68, and 70, did not extend beyond indirect detection.
Because Enzo does not contend that Applera infringes
claims 67, 68, and 70 under the proper reading of the
claims we provided in Enzo II, we affirm the district
court’s judgment as to claims 67, 68, and 70.
ENZO BIOCHEM INC. v. APPLERA CORP. 9
B. Doctrine of Equivalents for Claims 1 and 8
Enzo concedes that Applera does not literally infringe
claims 1 and 8 under our claim construction in Enzo II.
See id. at *15. But Enzo argues that Applera infringes
these claims under the doctrine of equivalents. Enzo
contends that the district court erred in granting sum-
mary judgment of noninfringement because there is a
genuine dispute of material fact regarding whether Ap-
plera’s accused products infringe under the doctrine of
equivalents.
“[A] product or process that does not literally infringe
upon the express terms of a patent claim may nonetheless
be found to infringe if there is ‘equivalence’ between the
elements of the accused product or process and the
claimed elements of the patented invention.” Warner-
Jenkinson Co. v. Hilton Davis Chem. Co., 520 U.S. 17, 21
(1997). “What constitutes equivalency must be deter-
mined against the context of the patent, the prior art, and
the particular circumstances of the case.” Id. at 24 (quot-
ing Graver Tank & Mfg. Co. v. Linde Air Prods. Co., 339
U.S. 605, 609 (1950)).
A party can show infringement under the doctrine of
equivalents if every limitation of the asserted claim,
including a limitation’s “equivalent,” is found in the
accused product, “where an ‘equivalent’ differs from the
claimed limitation only insubstantially.” Ethicon Endo-
Surgery, Inc. v. U.S. Surgical Corp., 149 F.3d 1309, 1315
(Fed. Cir. 1998). “Whether a component in the accused
subject matter performs substantially the same function
as the claimed limitation in substantially the same way to
achieve substantially the same result may be relevant to
this determination.” Id.
But we also have explained that “the concept of
equivalency cannot embrace a structure that is specifical-
ly excluded from the scope of the claims.” Dolly, Inc. v.
Spalding & Evenflo Cos., 16 F.3d 394, 400 (Fed. Cir.
10 ENZO BIOCHEM INC. v. APPLERA CORP.
1994). The doctrine of equivalents also cannot “render[] a
claim limitation inconsequential or ineffective.” Akzo
Nobel Coatings, Inc. v. Dow Chem. Co., 811 F.3d 1334,
1342 (Fed. Cir. 2016). And, as the Supreme Court has
stated, “if a theory of equivalence would entirely vitiate a
particular claim element, partial or complete judgment
should be rendered by the court, as there would be no
further material issue for the jury to resolve.” Warner-
Jenkinson, 520 U.S. at 39 n.8.
Enzo claims that the district court “misconstrued” its
expert declaration and improperly drew inferences in
favor of Applera, rather than Enzo, when ruling on the
motion for summary judgment. Appellant’s Br. 25.
According to Enzo, the district court could not have grant-
ed summary judgment on the doctrine of equivalents in
the face of its expert’s “reasoned and reasonable func-
tion/way/result comparison of the accused products with
the invention of claim 1.” Id. at 26. Enzo also argues that
its “asserted equivalent” was not disclaimed through the
’767 patent’s criticism of radioactive labeling. Id. at 29.
Enzo acknowledges that it critiqued radioactive labels for
“their hazards, inconvenience, cost and shelf life,” but it
argues that the district court did not explain the rele-
vance of these issues to the doctrine of equivalents theory
put forward by Enzo. Id. Enzo asserts that it is not
“asserting a scope of equivalents broad enough to encom-
pass all directly detectable labels including radioactive
ones”; instead, it focused on a particular subset of direct
detection. Id.
We conclude that the district court correctly granted
summary judgment in favor of Applera. The district court
explained that the patent “describes its method of indirect
detection as a superior means of detection as compared to
direct detection, with ‘detection capacities equal to or
greater than products which utilize’ direct detection.”
District Court Decision, 2016 U.S. Dist. LEXIS 20904, at
*21 (quoting Enzo II, 780 F.3d at 1155). As the district
ENZO BIOCHEM INC. v. APPLERA CORP. 11
court aptly concluded after its analysis, “[Enzo] cannot
now claim that indirect and direct detection are insub-
stantially different, and no jury could so find.” Id. at *22.
Indeed, Enzo’s attempt to reframe its infringement
case under the doctrine of equivalents runs headfirst into
our decision in Enzo II. In that decision, we reviewed the
claims and the specification to find that the claims cov-
ered only indirect detection. Enzo II, 780 F.3d at 1154–
55. We explained that “[t]he specification provides addi-
tional support that claim 1 covers only indirect detection.”
Id. at 1155. We also stated that the specification does not
“support[] the inclusion of direct detection, even when
extrinsic expert testimony is considered.” Id. at 1156.
And the specification’s “only discussion of direct detec-
tion . . . was exclusively in the context of discussing how
indirect detection is a superior method.” Id. at 1155.
Based on these facts, we were “persuaded that the inven-
tors were claiming only indirect detection.” Id. at 1156.
Our decision in Enzo II, therefore, focused entirely on
the conclusion that the asserted claims do not include
direct detection in part because they excluded direct
detection. Enzo’s attempt to incorporate direct detection
methods now through the doctrine of equivalents fails. In
Dolly, we concluded that “the concept of equivalency
cannot embrace a structure that is specifically excluded
from the scope of the claims.” 16 F.3d at 400. Applying
this concept to that case, we noted that “[a] stable rigid
frame assembled from the seat and back panels is not the
equivalent of a separate stable rigid frame which the
claim language specifically limits to structures exclusive
of seat and back panels.” Id. Indeed, we found that the
district court erred by “failing to give effect to this claim
limitation in applying the doctrine of equivalents.” Id.
The same principle applies in this case; the concept of
equivalency cannot embrace direct detection because it is
“specifically excluded from the scope of the claims,” id., as
we found in Enzo II. Including direct detection as an
12 ENZO BIOCHEM INC. v. APPLERA CORP.
equivalent of indirect detection would render meaningless
the claim language on which we based our decision in
Enzo II; direct detection cannot be an equivalent of indi-
rect detection in relation to these patent claims. See Akzo
Nobel Coatings, 811 F.3d at 1342 (“Under the doctrine of
equivalents, an infringement theory thus fails if it renders
a claim limitation inconsequential or ineffective.”); Am.
Calcar, Inc. v. Am. Honda Motor Co., 651 F.3d 1318,
1338–39 (Fed. Cir. 2011) (concluding that a theory of
equivalence was “legally insufficient” because it “would
vitiate [the] claim limitation by rendering it meaningless”
to find that “a signal from one source” was equivalent to
“signals from a plurality of sources”).
As the district court correctly held, no reasonable jury
could find, even under the doctrine of equivalents, that
Applera’s accused products using direct detection infringe
Enzo’s patent claiming indirect detection.
III. CONCLUSION
For the foregoing reasons, we affirm the district
court’s judgment in this case.
AFFIRMED