Court Opinion

ID: 2786372
Source: CourtListenerOpinion
Date Created: 2015-03-16 16:01:12.313809+00
Date Added: 2024-06-11T11:28:39.675545
License: Public Domain

United States Court of Appeals
      for the Federal Circuit
                ______________________

  ENZO BIOCHEM INC., ENZO LIFE SCIENCES,
          INC., YALE UNIVERSITY,
              Plaintiffs-Appellees

                           v.

          APPLERA CORP., TROPIX, INC.,
               Defendants-Appellants
              ______________________

                      2014-1321
                ______________________

    Appeal from the United States District Court for the
District of Connecticut in No. 3:04-CV-00929, Judge Janet
Bond Arterton.
                 ______________________

                Decided: March 16, 2015
                ______________________

   L. GENE SPEARS, Baker Botts, LLP, Houston, TX, ar-
gued for plaintiffs-appellees.  Also represented by
MICHAEL HAWES.

    CARTER GLASGOW PHILLIPS, Sidley Austin LLP, Wash-
ington, DC, argued for defendants-appellants.    Also
represented by JENNIFER J. CLARK; ROBERT N. HOCHMAN,
Chicago, IL.
                ______________________
2                        ENZO BIOCHEM INC.   v. APPLERA CORP.

    Before PROST, Chief Judge, NEWMAN and LINN, Circuit
                          Judges.
      Opinion for the court filed by Chief Judge PROST.
     Dissenting opinion filed by Circuit Judge NEWMAN.
PROST, Chief Judge.
     This appeal arises from the judgment of the United
States District Court for the District of Connecticut
following a jury trial on issues of infringement and inva-
lidity of U.S. Patent 5,449,767 (“’767 patent”). The Plain-
tiffs, Enzo Biochem Inc., Enzo Life Sciences, Inc., and
Yale University (collectively “Enzo”), asserted claims 1, 8,
67, 68, and 70 of the ’767 patent against the Defendant
Applera Corp. and Tropix, Inc. (“Applera”). Relevant to
this appeal, the jury returned a verdict for Enzo finding
that Applera directly infringed all of the asserted claims,
that Applera induced its customers to infringe all of the
asserted claims, and that the claims at issue were not
proven by clear and convincing evidence to lack enable-
ment or written description. The district court denied
Applera’s post-trial motions and granted Enzo’s motion
for award of pre- and post-judgment interest, as modified.
Applera appeals the district court’s claim construction,
which construes the claims at issue to cover both direct
and indirect detection of a signalling moiety, and in the
alternative appeals the district court’s denial of Applera’s
post-trial motion that the asserted claims were not ena-
bled and lacked written description.
    Because we agree with Applera that the district court
erred in its claim construction by finding that the claims
at issue covered direct detection, we reverse the district
court’s claim construction, vacate the judgment of in-
fringement, and remand for further findings under the
claim construction articulated herein.
ENZO BIOCHEM INC.   v. APPLERA CORP.                      3

                        BACKGROUND
    This case involves the use of nucleotide probes that al-
low a scientist to detect, monitor, localize, or isolate
nucleic acids when present in extremely small quantities,
as is necessary for the sequencing of deoxyribonucleic acid
(DNA).
    As this court discussed extensively in a previous iter-
ation of this case:
        DNA and RNA are composed of a series of
   units, called “nucleotides.” Each nucleotide is
   composed of a nitrogenous base, a pentose sugar,
   and a phosphate group. The phosphate group of
   one nucleotide forms a covalent bond with the
   pentose sugar of an adjacent nucleotide, thereby
   linking the nucleotides along a “sugar-phosphate
   backbone.” Aside from linking the nucleotide
   units into a polynucleotide strand, the sugar-
   phosphate backbone provides structural support
   for the nitrogenous bases. The bases fall into two
   categories: pyrimidines and purines. Pyrimidines
   include cytosine (“C”), thymine (“T”), and uracil
   (“U”). Purines include adenine (“A”) and guanine
   (“G”). DNA contains the bases adenine, thymine,
   cytosine, and guanine; RNA also includes adenine,
   cytosine, and guanine, but contains the base ura-
   cil in place of thymine. Two strands of DNA or
   RNA having complementary bases will bind, or
   “hybridize,” to form a double-stranded complex, or
   “hybrid,” which is held together by hydrogen
   bonds between complementary bases. In DNA,
   adenine on one strand binds to thymine on the
   other; in RNA, adenine binds to uracil; and in
   both DNA and RNA, cytosine binds to guanine.
   The process of forming a double-stranded hybrid
   is called “hybridization.” The reverse process, re-
4                        ENZO BIOCHEM INC.   v. APPLERA CORP.

    sulting in two separate strands, is called “dena-
    turation.”
         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.
        Labeling of nucleic acids has been accom-
    plished using a variety of chemical entities. For
    example, with radioactive labels, an isotope of hy-
    drogen ( 3H), phosphorous ( 32P), or carbon ( 14C) is
    substituted for a non-radioactive atom within the
    probe, and the isotope is then detected using a ra-
    diation detector. But radioactive labels have
    drawbacks. As explained in the . . . ’767 . . . pa-
    tent, radioactive labels are “potentially hazard-
    ous,” “expensive to purchase and use,” and “often
    very unstable.”
Enzo Biochem, Inc. v. Applera Corp., 599 F.3d 1325, 1328
(Fed. Cir. 2010).
    DNA sequencing relies on the aforementioned princi-
ples, except with the goal of determining the order of base
pairs in an unknown DNA sequence rather than deter-
mining whether a known DNA sequence is present. Until
ENZO BIOCHEM INC.   v. APPLERA CORP.                       5

recently, the predominant method of DNA sequencing,
and the method relevant to this case, was the Sanger
method. The Sanger method requires that a sample of
the DNA strand to be sequenced be placed in a solution
that includes nucleotides, a primer (short piece of DNA),
and a polymerase enzyme. Once combined, the primer
hybridizes to a portion of the unknown DNA sequence.
Then, starting at the primer, the polymerase enzyme
attaches individual complementary nucleotides and
covalently attaches them to the proceeding nucleotide in
the strand.
    The key to the Sanger method is that a small portion
of the nucleotides added to solution are special nucleo-
tides, capable of preventing the polymerase enzyme from
adding any additional nucleotides to the DNA strand.
These special nucleotides are called dideoxyterminators.
The incorporation of the dideoxyterminators is random,
and thus allows for the synthesized DNA strands to be of
varying lengths. The newly synthesized complementary
strands are then sorted from shortest to longest. One
then identifies the dideoxyterminator for each strand
length. By knowing strand length and the strand’s dide-
oxyterminator, one can determine the nucleotide sequence
of the unknown DNA strand.
     Just as with DNA probes, dideoxyterminators are de-
tected either by direct or indirect detection. And just as
when using DNA probes, detecting dideoxyterminators
through direct detection, i.e., with radioactive isotopes, is
potentially hazardous and expensive. To avoid these
drawbacks, nucleotide probes that do not rely on tradi-
tional radioactive labels were developed. The ’767 patent
is directed toward these new nucleotide probes.
    Claim 1 of the ’767 patent is directed to a compound
in which a nitrogenous base “B” is covalently attached,
“directly” or through a “linkage group” (represented by
the dotted line), to a chemical moiety “A.” ’767 patent col.
6                          ENZO BIOCHEM INC.   v. APPLERA CORP.

30 l. 59-col. 31 l. 11. The linkage group is not recited in
the independent claim in structural terms, but is instead
described as “not substantially interfer[ing] with the
characteristic ability of the oligo- or polynucleotide to
hybridize with a nucleic acid and . . . not substantially
interfer[ing] with formation of the signalling moiety or
detection of the detectable signal . . . .” Id. at col. 31 ll. 1-
7.
    Claim 1 is representative and reads:
    An oligo- or polynucleotide containing a nucleotide
    having the structure:

    wherein B represents a 7-deazapurine or a pyrim-
    idine moiety covalently bonded to the C1´-position
    of the sugar moiety, provided that whenever B is a
    7-deazapurine, the sugar moiety is attached at the
    N9-position of the 7-deazapurine, and whenever B
    is a pyrimidine, the sugar moiety is attached at
    the N1-position of the pyrimidine;
    wherein A comprises at least three carbon atoms
    and represents at least one component of a signal-
    ing moiety capable of producing a detectable sig-
    nal;
    wherein B and A are covalently attached directly
    or through a linkage group that does not substan-
    tially interfere with the characteristic ability of
    the oligo- or polynucleotide to hybridize with a nu-
    cleic acid and does not substantially interfere with
ENZO BIOCHEM INC.   v. APPLERA CORP.                      7

   formation of the signalling moiety or detection of
   the detectable signal, provided also that if B is 7-
   deazapurine, A or the linkage group is attached to
   the 7-position of the deazapurine, and if B is py-
   rimidine, A or the linkage group is attached to
   the 5-position of the pyrimidine;
   wherein one of x and y represents

   and the other of x and y is absent or represents
   –OH or –H; and wherein z represents H– or HO–.
    At a Markman hearing, the district court construed
disputed claim terms for several patents, including
the ’767 patent. Of significance here, the district court
construed two phrases of claim 1 of the ’767 patent. First,
the district court construed the phrase “A comprises at
least three carbon atoms and represents at least one
component of a signalling moiety capable of producing a
detectable signal” as “A comprises at least three carbon
atoms and is one or more parts of a signalling moiety,
which includes, in some instances, the whole signalling
moiety.” Enzo Biochem, Inc. v. Applera Corp., No. 3:04-
CV-929, 2006 WL 2927500, at *2, *4 (D. Conn. Oct. 12,
2006). Second, the district court construed the phrase
“signalling moiety” as “a chemical entity capable of pro-
ducing a detectable signal.” Id. Because the district
court’s construction does not require that any additional
components be attached to “A” to form the signalling
moiety, and that a “signalling moiety” may itself produce
a detectable signal, the district court’s claim construction
allows for direct detection. In other words, because the
claim was construed in such a manner that no additional
8                        ENZO BIOCHEM INC.   v. APPLERA CORP.

steps are required to detect the compound, it can be
directly detected. This is in contrast with a claim con-
struction that would limit the claim to indirect detection
by requiring that another compound be added to “A” in
order for it to be detectable. Thus, the district court’s
construction allowed for both direct and indirect detection
of the claimed compound.
    The case then proceeded to a jury trial, where the jury
found that the asserted claims were infringed and that
the ’767 patent was not invalid for lack of written descrip-
tion and enablement. The district court then denied
Applera’s post-trial motions.
    Applera timely appealed to this court, arguing that
the district court erred in its claim construction or in the
alternative that the asserted claims were invalid for lack
of written description or enablement. This court has
jurisdiction over this case under 28 U.S.C. § 1295(a)(1).
                       DISCUSSION
    While the ultimate construction of a claim term is a
legal question reviewed de novo, underlying factual
determinations made by the district court are reviewed
for clear error. Teva Pharm. USA, Inc. v. Sandoz, Inc.,
No. 13-854, 2015 WL 232131, at *11 (U.S. Jan. 20, 2015).
Specifically, “when the district court reviews only evi-
dence intrinsic to the patent (the patent claims and
specifications, along with the patent’s prosecution histo-
ry), the judge’s determination will amount solely to a
determination of law, and the Court of Appeals will
review that construction de novo.” Id. at *10. However,
when the district court looks beyond the intrinsic evidence
and consults extrinsic evidence, for example to under-
stand the relevant science, these subsidiary fact findings
are reviewed for clear error. Id.
    To the extent possible, “the words of a claim are gen-
erally given their ordinary and customary meaning.”
ENZO BIOCHEM INC.   v. APPLERA CORP.                        9

Phillips v. AWH Corp., 415 F.3d 1303, 1312 (Fed. Cir.
2005) (en banc) (internal quotation marks omitted). The
“ordinary and customary meaning of a claim term” is that
meaning that a person of ordinary skill in the art in
question, at the time of the invention, would have under-
stood the claim to mean. Id. at 1313. “Because the mean-
ing of a claim term as understood by persons of skill in
the art is often not immediately apparent, and because
patentees frequently use terms idiosyncratically,” the
court also looks to “the remainder of the specification, the
prosecution history, and extrinsic evidence concerning
relevant scientific principles, the meaning of technical
terms, and the state of the art.” Id. However, when doing
so the court must stay ever vigilant to avoid reading
limitations from the specification into the claim. Id.
    It is with these tenets in mind that the court now re-
views the district court’s Markman order.
    We begin with the language of the claims. 1 Claim 1 of
the ’767 patent states that “A” “comprises at least three
carbon atoms and represents at least one component of a
signaling moiety capable of producing a detectable signal”
and is attached to “B” so that it “does not substantially
interfere with formation of the signalling moiety.” ’767
patent col. 30 l. 66-col. 31 l. 6 (emphasis added). First, the
phrase “at least one component of a signalling moiety”
indicates that the signalling moiety is composed of multi-
ple parts as the term “component” in and of itself indi-
cates a multipart system. Thus, construing the phrase to
allow for a single-component system, as the district court
did here, would read out the phrase “component of a
signalling moiety” and would thus impermissibly broaden

    1   The court finds that Enzo’s argument that Ap-
plera waived its ability to appeal the district court’s claim
construction meritless given the posture of the previous
appeal.
10                       ENZO BIOCHEM INC.   v. APPLERA CORP.

the claim. See Bicon, Inc. v. Straumann Co., 441 F.3d
945, 950 (Fed. Cir. 2006) (“Claims are interpreted with an
eye toward giving effect to all terms in the claim.”).
    Second, the claim language requires that “A” be at-
tached either directly or through a linkage group that
“does not substantially interfere with formation of the
signalling moiety.” ’767 patent col. 31 ll. 5-6. The plain
reading of this phrase is that “A” cannot be the whole
signalling moiety, as the claimed compound does not
include a formed signalling moiety. In other words, if “A”
alone could be the signalling moiety, as the district court
found, the requirement that “A” not interfere with the
formation of the signalling moiety would be read out of
the claim, as the signalling moiety would be formed by the
sole presence of “A.”
     Enzo urges that we should hold that the inventors’ in-
clusion of the term “at least one of” allows for both direct
and indirect detection. Enzo cites to Howmedica Osteon-
ics Corp. v. Wright Medical Technology, Inc., 540 F.3d
1337 (Fed. Cir. 2008), to support this argument. Specifi-
cally, Enzo argues that Howmedica illustrates that pa-
tentees use open-ended language, such as “at least one,”
to encompass multiple embodiments. Howmedica dealt
with a patent for a prosthetic knee with a tibular and
femoral component. 540 F.3d at 1340. At issue was the
correct construction for a claim reciting “the femoral
component including at least one condylar element”
conforming to the geometric limitations specified in the
claim. Id. at 1344. There was no dispute that the claim
could cover a unicondylar prosthesis, but the parties
disagreed as to whether both condyles of a bicondylar
femoral component must meet the geometric limitations
of the claim. Id. We agreed with the district court that
the phrase “at least one” in the claim language means
“one or more” condylar elements are required, but held
that the claim does not require both condyles of a bicondy-
lar femoral component to conform to the geometric limita-
ENZO BIOCHEM INC.    v. APPLERA CORP.                              11

tions of the claim, noting that the claim says that “the
condylar element” must have the specified geometry,
instead of “both” or “each” condylar element. Id.
    Howmedica is inapposite. Here, the dispute is wheth-
er “A” can comprise the entirety of “a signalling moiety”
despite the claim language that “A” is a “component of a
signalling moiety.” Howmedica was not concerned with
whether “the femoral component” could be comprised
solely of a condylar element, but whether the femoral
component could include one or more condylar elements,
and whether each must conform to the geometric limita-
tions. Thus, unlike in Howmedica where the claim did
not require the prosthetic knee to have more than one
condylar element, here the plain reading of the disputed
claim term requires that a signalling moiety be composed
of components, of which at least one is “A.”
     The specification provides additional support that
claim 1 covers only indirect detection. First, throughout
the specification, “A” is described as being capable of
forming a signalling moiety only in conjunction with other
chemicals, never that “A” alone can be a signalling moie-
ty. See ’767 patent (Abstract), col. 3 ll. 47-53, col. 5 ll. 33-
35, col. 7 ll. 28-30, col. 8 ll. 4-8, col. 11 ll. 5-7, col. 16 ll. 63-
65. Second, the background portion of the specification
further describes the invention as a “series of novel nucle-
otide derivatives that contain biotin, iminobiotin, lipoic
acid, and other determinants attached covalently to the
pyrimidine or purine ring” and explains that these nucleo-
tides “will interact specifically and uniquely with proteins
such as avidin or antibodies.” Id. at col. 3 ll. 2-3. The
specification then goes on to describe this interaction as
being used “for the detection and localization of nucleic
acid components in many of the procedures currently used
in biomedical and recombinant-DNA technologies.” Id. at
col. 3 ll. 3-9. In other words, the patent describes how
“A,” a biotin, iminobiotin, or lipoic acid, forms a detectable
unit, i.e., a signalling moiety, upon interaction with avidin
12                       ENZO BIOCHEM INC.   v. APPLERA CORP.

or antibodies. Third, the specification’s only discussion of
direct detection, here radioactive labeling, was exclusively
in the context of discussing how indirect detection is a
superior method. The specification not only discusses the
limitations and drawbacks of using radioactive labeling,
but states that the claimed compounds can be used “as an
alternative to radioisotopes for detection and localization”
and that these compounds have “detection capacities
equal to or greater than products which utilize radioiso-
topes and often can be performed more rapidly and with
greater resolving power.” Id. at col. 3 ll. 5-13.
    At oral argument, Enzo was repeatedly asked to point
the court to a location in the specification that supports
its proposed claim construction. In response, Enzo cited
to column 14 line 63 to column 15 line 12 and column 8.
Oral       Arg.       at        14:27-14:52,      19:15-19:42,
http://oralarguments.cafc.uscourts.gov/default.aspx?fl=20
14-1321.mp3. The first cited section of the specification,
however, refers to experimentation conducted to deter-
mine whether biotin may be successfully attached to
nucleotides, i.e., whether the invention may be synthe-
sized, not whether the claimed invention may utilize
direct detection. The second citation also provides no
support for Enzo’s argument. The section reads that “A
may be any moiety which has at least three carbon atoms
and is capable of forming a detectable complex with a
polypeptide when the modified nucleotide is incorporated
into a double stranded duplex containing either deoxyri-
bonucleic or ribonucleic acid.” ’767 patent col. 8 ll. 4-8
(emphasis added). The section continues to discuss how
“A” may be ligands that interact with appropriate anti-
bodies. See id. at col. 8 ll. 9-45. Thus, the section does not
discuss direct detection, but instead discusses indirect
detection. In fact, at oral argument Enzo agreed that
nowhere in the specification—including the sections it
had cited—were ligands described as being directly de-
tectable. Instead, Enzo argued that extrinsic expert
ENZO BIOCHEM INC.   v. APPLERA CORP.                      13

testimony indicated that the described ligands could be
detected through various methods, such as proton NMR
spectroscopy. However, the expert testimony cited by
Enzo does not discuss whether ligands, such as biotin, as
attached to the dideoxyterminator, could be directly
detected, but instead whether one could directly detect a
“clean pure solution of biotin” in a test tube, a fundamen-
tally different question. J.A. 11290-91. Thus, neither
section of the ’767 patent specification cited by Enzo
supports the inclusion of direct detection, even when
extrinsic expert testimony is considered.
    We have long recognized the “distinction between us-
ing the specification to interpret the meaning of a claim
and importing limitations from the specification into the
claim can be a difficult one to apply in practice.” Phillips,
415 F.3d at 1323 (citing Comark Commc’ns, Inc. v. Harris
Corp., 156 F.3d 1182, 1186-87 (Fed. Cir. 1998). Here, we
are using the specification to more fully understand what
the patentee claimed. See id. at 1315 (“[T]he best source
for understanding a technical term is the specification
from which it arose, informed, as needed, by the prosecu-
tion history.” (internal brackets and quotation marks
omitted)). Throughout the ’767 patent, the inventors
repeatedly emphasized that “A” in combination with other
chemicals, forms a signalling moiety not that “A” itself
can be a signalling moiety. Therefore, we are persuaded
that the inventors were claiming only indirect detection.
    The district court concluded, based on expert testimo-
ny, that example 9 in the specification was an example of
direct detection; however, this argument was not raised
by Enzo either in its briefing on appeal or during oral
argument. Nevertheless, even if we were to consider the
district court’s finding, which would be subject to review
for clear error under Teva, this sole factual finding does
not override our analysis of the totality of the specifica-
tion, which clearly indicates that the purpose of this
14                       ENZO BIOCHEM INC.   v. APPLERA CORP.

invention was directed towards indirect detection, not
direct detection.
     The district court additionally relied upon claim dif-
ferentiation to support its finding that the claims at issue
cover both direct and indirect detection. Enzo, 2006 WL
2927500, at *3. The district court found that dependent
claims 67, 68, and 70 of the ’767 patent involved direct
detection and therefore independent claim 1 must not be
limited to indirect detection. Id. However, dependent
claims cannot broaden an independent claim from which
they depend. Curtiss-Wright Flow Control Corp. v. Velan,
Inc., 438 F.3d 1374, 1381 (Fed. Cir. 2006) (“In the most
specific sense, claim differentiation refers to the presump-
tion that an independent claim should not be construed as
requiring a limitation added by a dependent claim.”
(citing Nazomi Commc’ns, Inc. v. Arm Holdings, PLC, 403
F.3d 1364, 1370 (Fed. Cir. 2005)) (internal quotation
marks omitted). Thus, as claim 1 is limited to indirect
detection by its own plain meaning, it would be inappro-
priate to use the doctrine of claim differentiation to
broaden claim 1 to include a limitation imported from a
dependent claim, such as direct detection.
                       CONCLUSION
    The district court erred in construing the disputed
claims of the patent-in-suit to cover both direct and indi-
rect detection. Accordingly, we reverse the district court’s
claim construction, vacate the district court’s finding of
infringement, and remand to the district court with
instruction to determine, consistent with the analysis in
this opinion, whether the accused product infringes.
  REVERSED-IN-PART, VACATED-IN-PART, AND
                REMANDED
                          COSTS
     Costs are awarded to Applera.
  United States Court of Appeals
      for the Federal Circuit
                 ______________________

  ENZO BIOCHEM INC., ENZO LIFE SCIENCES,
        INC., AND YALE UNIVERSITY,
               Plaintiffs-Appellees,

                            v.

        APPLERA CORP. AND TROPIX, INC.,
             Defendants-Appellants.
             ______________________

                       2014-1321
                 ______________________

    Appeal from the United States District Court for the
District of Connecticut in No. 3:04-cv-00929-JBA, Judge
Janet Bond Arterton.
                ______________________

NEWMAN, Circuit Judge, dissenting.
    The principal issue discussed by the panel majority is
the construction of claim terms that determine whether
Patent No. 5,449,767 covers direct detection of the signal-
ing moiety, or only indirect detection. The distinction
between direct and indirect detection is stated to be
material to whether Applera infringes the ’767 patent.
The principal disputed term concerns the signaling struc-
ture represented by “A” in claim 1, and the meaning of “at
least one component,” here shown in boldface:
   1. An oligo- or polynucleotide containing a nucleo-
   tide having the structure:
2                        ENZO BIOCHEM INC.   v. APPLERA CORP.

        wherein B represents a 7-deazapurine or a py-
    rimidine moiety covalently bonded to the C1´-
    position of the sugar moiety, provided that when-
    ever B is a 7-deazapurine, the sugar moiety is at-
    tached at the N9-position of the 7-deazapurine,
    and whenever B is a pyrimidine, the sugar moiety
    is attached at the N1-position of the pyrimidine;
        wherein A comprises at least three carbon at-
    oms and represents at least one component of a
    signaling moiety capable of producing a detectable
    signal;
        wherein B and A are covalently attached di-
    rectly or through a linkage group that does not
    substantially interfere with the characteristic
    ability of the oligo- or polynucleotide to hybridize
    with a nucleic acid and does not substantially in-
    terfere with formation of the signalling moiety or
    detection of the detectable signal, provided also
    that if B is 7-deazapurine, A or the linkage group
    is attached to the 7-position of the deazapurine,
    and if B is pyrimidine, A or the linkage group is
    attached to the 5-position of the pyrimidine;
        wherein one of x and y represents
ENZO BIOCHEM INC.   v. APPLERA CORP.                       3

    and the other of x and y is absent or represents
    –OH or –H; and wherein z represents H– or HO–.
’767 Patent col. 30 l. 48 to col 31 l. 21 (emphases added).
The description of A in the specification includes the
following introduction:
        A may be any moiety which has at least three
    carbon atoms and is capable of forming a detecta-
    ble complex with a polypeptide when the modified
    nucleotide is incorporated into a double-stranded
    duplex containing either deoxyribonucleic or ribo-
    nucleic acid.
        A therefore may be any ligand which possess-
    es these properties, including haptens which are
    only immunogenic when attached to a suitable
    carrier, but are capable of interacting with appro-
    priate antibodies to produce complexes.
’767 Patent col. 8 ll. 4-14. The specification includes
further detail and several specific examples.
                         DISCUSSION
    The construction of the ’767 claims is not new to this
court. In the prior appeal, Enzo Biochem Inc. v. Applera
Corp., 599 F.3d 1325 (Fed. Cir. 2010), Applera had argued
that A is not the whole signaling moiety, but only part of
a multi-component signaling moiety. The district court
had found that: “‘A . . . is one or more parts of a signaling
moiety, which includes, in some instances, the whole
signaling moiety.’” Id. at 1330 (quoting Enzo Biochem,
Inc. v. Applera Corp., No. 3:04cv929, 2006 WL 2927500, at
*3 (D. Conn. Oct. 12, 2006)). My colleagues now hold that
the district court’s claim construction is incorrect, now
concluding that A cannot be the whole signaling moiety,
as a matter of grammatical construction of the claim
clause.
4                        ENZO BIOCHEM INC.   v. APPLERA CORP.

    My colleagues hold that the clause “at least one com-
ponent of a signaling moiety” requires, as a matter of
linguistics, “that the signalling moiety is composed of
multiple parts as the term ‘component’ in and of itself
indicates a multipart system.” Maj. Op. at 11 (emphasis
added). Thus the panel majority concludes that A can
never “include[], in some instances, the whole signaling
moiety,” contrary to the district court’s holding.
     My colleagues err. The rules of grammar and linguis-
tics, even in legal documents, do not establish that “at
least one” means two or more. Also, precedent has spoken
on this point and is directly contrary. See Howmedica
Osteonics Corp. v. Wright Med. Tech., Inc., 540 F.3d 1337,
1344 (Fed. Cir. 2008) (stating that “at least one” means
“one or more”).
    The district court construed “at least one” in accord-
ance with not only grammatical logic, but also with the
intrinsic record and the extrinsic evidence. The district
court found that the specification includes a specific
example of direct detection, citing the expert evidence:
    [T]he expert evidence indicates that Example 9
    could involve direct detection. See Reply Expert
    Report of Richard R. Sinden, Def. Ex. 13, ¶¶ 56,
    57 (citing Kricka Report, Def. Ex. 10, ¶ 30). Thus,
    importing into Claim 1 only the examples of indi-
    rect detection from the specification would skew
    the full illustrative range of all examples, result-
    ing in utilization of the specifications as “limita-
    tions” on Claim 1 rather than as aids for
    understanding technical terms.
Enzo Biochem, 2006 WL 2927500, at *3. The district
court also found that claims 67, 68 and 70 of the ’767
patent “teach direct detection, with ‘A compris[ing] an
indicator molecule.’” Id. The district court observed that
claim 67 of the ’767 patent “teaches that ‘A comprises an
indicator molecule,’ and Claims 68 and 70 teach that ‘An
ENZO BIOCHEM INC.   v. APPLERA CORP.                       5

oligo- or polynucleotide of claim 67 where said indicator is
fluorescent, electron dense, or an enzyme capable of
depositing insoluble reaction products,’ or ‘is selected from
the group consisting of fluorescein and rhodamine.’” Id.
at *4. The district court stated that “in the context of all
the dependent claims taken together, the Court sees no
basis for inferring from the word ‘comprise’ in certain
claims that A must have more than one component, as
opposed to suggesting that A may have more than one
component.” Id. Applera’s expert Dr. Kricka had so
conceded on cross-examination, and the district court
summarized, “the jury was entitled to credit Dr. Kricka’s
testimony that several parts of the original application
disclosed compounds that allowed for direct detection.”
Enzo Biochem, Inc. v. Applera Corp., No. 3:04cv929, 2013
WL 3965305, at *8 (D. Conn. Aug. 1, 2013). These factual
findings are entitled to deference, in accordance with the
Court’s instruction in Teva Pharmaceuticals USA, Inc. v.
Sandoz, Inc., 135 S. Ct. 831 (2015).
    My colleagues on this appeal do not point to any con-
trary evidence; they simply rule that grammar requires
that if the signaling moiety is “at least one component”
then there must be at least two components. From this,
my colleagues rule that “claim 1 covers only indirect
detection,” Maj. Op. at 11, ignoring the testimony and the
district court’s findings and the jury verdict based on the
evidence at trial.
    In Teva, the Court established that, when construing
claims, appropriate deference must be given to the find-
ings of the district court. The district court received some
conflicting testimony, along with concessions on cross-
examination, from which the court concluded that “at
least one component” may include “the whole signaling
moiety.” My colleagues show error of neither fact nor law
in the court’s findings and conclusions.
6                        ENZO BIOCHEM INC.   v. APPLERA CORP.

    Grounds for reversal of the court’s construction that
the claims include direct as well as indirect detection have
not been shown. From the panel majority’s contrary
ruling, I respectfully dissent.