Source: s3://data.kl3m.ai/documents/govinfo/USCOURTS/USCOURTS-ca13-14-01321/USCOURTS-ca13-14-01321-0/pdf.json

Nature of Suit Code: 830
Nature of Suit: Patent
Cause of Action: 

---

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, argued for plaintiffs-appellees. Also represented by 

MICHAEL HAWES. 

CARTER GLASGOW PHILLIPS, Sidley Austin LLP, Washington, DC, argued for defendants-appellants. Also 

represented by JENNIFER J. CLARK; ROBERT N. HOCHMAN, 

Chicago, IL. 

______________________ 

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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 invalidity of U.S. Patent 5,449,767 (“’767 patent”). The Plaintiffs, 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 enablement 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 enabled 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 infringement, and remand for further findings under the 

claim construction articulated herein. 

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ENZO BIOCHEM INC. v. APPLERA CORP. 3

BACKGROUND

This case involves the use of nucleotide probes that allow 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 iteration 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 sugarphosphate 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 uracil 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, reCase: 14-1321 Document: 49-2 Page: 3 Filed: 03/16/2015
4 ENZO BIOCHEM INC. v. APPLERA CORP. 

sulting in two separate strands, is called “denaturation.” 

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 entity, called a “label,” can be attached to or incorporated 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 detection”) or from a secondary chemical agent that is 

bound to the label (referred to as “indirect detection”). If a signal is detected from the sample after 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 accomplished using a variety of chemical entities. For 

example, with radioactive labels, an isotope of hydrogen ( 3H), phosphorous ( 32P), or carbon ( 14C) is 

substituted for a non-radioactive atom within the 

probe, and the isotope is then detected using a radiation detector. But radioactive labels have 

drawbacks. As explained in the . . . ’767 . . . patent, radioactive labels are “potentially hazardous,” “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 principles, except with the goal of determining the order of base 

pairs in an unknown DNA sequence rather than determining whether a known DNA sequence is present. Until 

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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 nucleotides, 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 dideoxyterminator, one can determine the nucleotide sequence 

of the unknown DNA strand. 

Just as with DNA probes, dideoxyterminators are detected 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 traditional 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. 

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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 pyrimidine 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 signaling moiety capable of producing a detectable signal;

wherein B and A are covalently attached directly 

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 interfere with 

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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 pyrimidine, 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 producing 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 

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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 construction 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 description 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 evidence intrinsic to the patent (the patent claims and 

specifications, along with the patent’s prosecution history), 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 understand the relevant science, these subsidiary fact findings 

are reviewed for clear error. Id. 

To the extent possible, “the words of a claim are generally given their ordinary and customary meaning.” 

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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 understood the claim to mean. Id. at 1313. “Because the meaning 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 reviews 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 multiple parts as the term “component” in and of itself indicates 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 Applera waived its ability to appeal the district court’s claim 

construction meritless given the posture of the previous 

appeal. 

 

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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 attached 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’ inclusion of the term “at least one of” allows for both direct 

and indirect detection. Enzo cites to Howmedica Osteonics Corp. v. Wright Medical Technology, Inc., 540 F.3d 

1337 (Fed. Cir. 2008), to support this argument. Specifically, Enzo argues that Howmedica illustrates that patentees 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 bicondylar femoral component to conform to the geometric limitaCase: 14-1321 Document: 49-2 Page: 10 Filed: 03/16/2015
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 whether “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 limitations. 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 moiety. 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 nucleotide derivatives that contain biotin, iminobiotin, lipoic 

acid, and other determinants attached covalently to the 

pyrimidine or purine ring” and explains that these nucleotides “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 

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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 radioisotopes 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 determine whether biotin may be successfully attached to 

nucleotides, i.e., whether the invention may be synthesized, 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 deoxyribonucleic 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 antibodies. 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 detectable. Instead, Enzo argued that extrinsic expert 

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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 fundamentally 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 using 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 prosecution 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 testimony, 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 specification, which clearly indicates that the purpose of this 

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14 ENZO BIOCHEM INC. v. APPLERA CORP. 

invention was directed towards indirect detection, not 

direct detection. 

The district court additionally relied upon claim differentiation 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 presumption 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 inappropriate 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 indirect 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.

Case: 14-1321 Document: 49-2 Page: 14 Filed: 03/16/2015
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 signaling 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 structure 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 nucleotide having the structure: 

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2 ENZO BIOCHEM INC. v. APPLERA CORP. 

 

 

 wherein B represents a 7-deazapurine or a pyrimidine 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 

signaling moiety capable of producing a detectable 

signal;

 wherein B and A are covalently attached directly 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 interfere 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 

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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 detectable complex with a polypeptide when the modified 

nucleotide is incorporated into a double-stranded 

duplex containing either deoxyribonucleic or ribonucleic acid.

A therefore may be any ligand which possesses these properties, including haptens which are 

only immunogenic when attached to a suitable 

carrier, but are capable of interacting with appropriate 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.

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4 ENZO BIOCHEM INC. v. APPLERA CORP. 

My colleagues hold that the clause “at least one component 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 linguistics, 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 accordance 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 indirect detection from the specification would skew 

the full illustrative range of all examples, resulting in utilization of the specifications as “limitations” 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 

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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 contrary 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 findings of the district court. The district court received some 

conflicting testimony, along with concessions on crossexamination, 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. 

Case: 14-1321 Document: 49-2 Page: 19 Filed: 03/16/2015
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.

Case: 14-1321 Document: 49-2 Page: 20 Filed: 03/16/2015