Petition for Writ of Certiorari — Enzo Life Sciences, Inc., Petitioner v. Roche Molecular Systems, Inc., et al.

Supreme Court briefFeb 26, 2020

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No. 19-____

IN THE

Supreme Court of the United States

ENZO LIFE SCIENCES, INC.,

Petitioner,

ROCHE MOLECULAR SYSTEMS, INC., ROCHE

DIAGNOSTICS CORPORATION, ROCHE DIAGNOSTICS

OPERATIONS, INC., ROCHE NIMBLEGEN, INC., BECTON

DICKINSON AND COMPANY, AKA Becton Dickson and

Company, BECTON DICKINSON DIAGNOSTICS INC., AKA

Becton Dickson Diagnostics, GENEOHM SCIENCES

INC., ABBOTT LABORATORIES, ABBOTT MOLECULAR,

INC.,

Respondents.

ON PETITION FOR WRIT OF CERTIORARI TO THE UNITED

STATES COURT OF APPEALS FOR THE FEDERAL CIRCUIT,

NOS. 17-2498, -2499, -2545, -2546

PETITION FOR A WRIT OF CERTIORARI

JOHN M. DESMARAIS

JUSTIN P.D. WILCOX,

Counsel of Record

DESMARAIS LLP

230 Park Avenue

New York, NY 10169

(212) 351-3400

jwilcox@desmaraisllp.com

PETER C. MAGIC

DESMARAIS LLP

101 California Street

San Francisco, CA

94111

(415) 573-1900

February 26, 2020

QUESTIONS PRESENTED

In light of a patent’s presumption of validity

under 35 U.S.C. § 282 and the concomitant clear

and convincing standard for proving invalidity,

may patent claims that cover a class be

invalidated as non-enabled under 35 U.S.C. § 112

based on a finding of high unpredictability in the

art despite an absence of any evidence of

inoperability within the class?

II. In concluding that the patent claims that cover a

class are invalid as non-enabled under 35 U.S.C.

§ 112 despite an absence of any evidence of

inoperability within the class, did the United

States Court of Appeals for the Federal Circuit

(“Federal Circuit”) erroneously shift the burden to

the patent owner to prove the claims were

enabled, and therefore valid, in violation of the

presumption of validity under 35 U.S.C. § 282?

PARTIES TO THE PROCEEDING

All parties to the proceeding are identified in the

caption.

RULE 29.6 STATEMENT

Petitioner Enzo Life Sciences, Inc. is a wholly

owned subsidiary of Enzo Biochem, Inc., which is a

publicly held company that owns 10 percent or more

of Enzo Life Sciences, Inc.’s stock.

RELATED PROCEEDINGS

The following federal cases are directly related to

this petition before this Court:



Enzo Life Sciences, Inc. v. Roche Molecular

Systems, Inc., Roche Diagnostics Corporation,

Roche Diagnostics Operations, Inc., Roche

Nimblegen, Inc., Becton, Dickinson and

Company, Becton Dickinson Diagnostics Inc.,

Geneohm Sciences Inc., Abbott Laboratories,

Abbott Molecular, Inc., Nos. 2017-2498, 20172499, 2017-2545, 2017-2546, United States

Court of Appeals for the Federal Circuit.

Judgment entered June 20, 2019.



Enzo Life Sciences, Inc. v. Abbott Laboratories

and Abbott Molecular, Inc., Nos. 12-cv-274, 13cv-225, United States District Court for the

District of Delaware. Judgment entered

September 1, 2017.



Enzo Life Sciences, Inc. v. Roche Molecular

Systems, Inc.; Roche Diagnostics Corporation;

Roche Diagnostics Operations, Inc.; and Roche

Nimblegen, Inc., No. 12-cv-106, United States

District Court for the District of Delaware.

Partial judgment entered on August 2, 2017.



Enzo Life Sciences, Inc. v. Becton, Dickinson

and Company; Becton Dickinson Diagnostics

Inc.; and Geneohm Sciences, Inc., No. 12-cv275, United States District Court for the

District of Delaware. Partial judgment

entered on July 31, 2017.

iii

TABLE OF CONTENTS

Page

QUESTIONS PRESENTED ........................................ i

PARTIES TO THE PROCEEDING ............................ii

RULE 29.6 STATEMENT ...........................................ii

RELATED PROCEEDINGS .......................................ii

TABLE OF APPENDICES......................................... vi

TABLE OF AUTHORITIES ...................................... vii

INTRODUCTION ........................................................ 1

OPINIONS BELOW .................................................... 2

JURISDICTION .......................................................... 2

PERTINENT STATUTORY PROVISIONS ............... 3

STATEMENT OF THE CASE .................................... 4

Background ........................................................ 4

Nucleic Acid Hybridization ......................... 4

The State Of The Art Before June 1982 .... 5

The Inventions Of The ’180 And ’405

Patents .................................................................. 6

II.

Prior Proceedings ......................................... 10

District Court ............................................ 10

Federal Circuit .......................................... 11

REASONS FOR GRANTING THE PETITION ....... 13

I. The Federal Circuit’s Invalidation Of The

Patents Without Evidence Of Inoperable Members

Of The Claimed Classes Undermines The

Statutory Burden And Standard Of Proof For

Challenges To Patent Validity. ............................. 13

To Show That A Patent Is Invalid, A

Challenger Must Meet A Clear And Convincing

Standard Of Proof. .............................................. 13

The Federal Circuit Applies An “Undue

Experimentation” Test To Patent Validity

Challenges Under The Enablement Requirement

Of § 112. .............................................................. 15

The Federal Circuit Applies An EightFactor Factual Test To Evaluate The Degree Of

Experimentation. ................................................ 18

In The Present Case, The Predictability Of

The Art Controlled The Federal Circuit’s

Analysis Of The Wands Factors, Despite A Lack

Of Evidence Of Inoperable Embodiments Within

The Claimed Class. ............................................. 19

The Federal Circuit’s Invalidation Of

Patent Claims Without Evidence Of Inoperable

Embodiments In The Claimed Class Warrants

Review And Reversal. ......................................... 23

CONCLUSION .......................................................... 27

TABLE OF APPENDICES

Page

APPENDIX A — Opinion Of The United States

Court Of Appeals For The Federal Circuit, Filed

June 20, 2019............................................................. 1a

APPENDIX B — Memorandum Opinion Of The

United States District Court For The District Of

Delaware, Filed August 15, 2017............................ 19a

APPENDIX C — Memorandum Opinion Of The

United States District Court For The District Of

Delaware, Filed June 28, 2017 ............................... 44a

APPENDIX D — Denial Of Rehearing Of The United

States Court Of Appeals For The Federal Circuit,

Filed October 29, 2019 ............................................ 67a

TABLE OF AUTHORITIES

Page

Cases

Alcon Research Ltd. v. Barr Labs., Inc.,

745 F.3d 1180 (Fed. Cir. 2014) ............ 14, 15, 19, 24

Allergan, Inc. v. Sandoz Inc.,

796 F.3d 1293 (Fed. Cir. 2015) ........................ 14, 15

Application of Angstadt,

537 F.2d 498 (C.C.P.A. 1976) ................................. 17

Application of Eltgroth,

419 F.2d 918 (C.C.P.A. 1970) ................................. 15

Atlas Powder Co. v. E.I. du Pont De Nemours & Co.,

750 F.2d 1569 (Fed. Cir. 1984) ........................ 13, 16

Bene v. Jeantet,

129 U.S. 683 (1889) ................................................ 18

Bonito Boats, Inc. v. Thunder Craft Boats, Inc.,

489 U.S. 141 (1989) ................................................ 26

Coffin v. Ogden,

85 U.S. 120 (1873) .................................................. 27

Consol. Elec. Light Co. v. McKeesport Light Co.,

159 U.S. 465 (1895) ................................................ 18

Fields v. Conover,

443 F.2d 1386 (C.C.P.A. 1971) ............................... 16

Howard v. Detroit Stove Works,

150 U.S. 164 (1893) ................................................ 18

Idenix Pharmaceuticals LLC v. Gilead Sciences, Inc.,

941 F.3d 1149 (Fed. Cir. 2019) ........................ 24, 25

Microsoft Corp. v. i4i Ltd.,

564 U.S. 91 (2011) ................................ 13, 14, 26, 27

vii

Minerals Separation v. Hyde,

242 U.S. 261 (1916) ......................................... 18, 27

W.L. Gore & Assocs., Inc. v. Garlock, Inc.,

721 F.2d 1540 (Fed. Cir. 1983) ........................ 16, 18

Wyeth & Cordis Corp. v. Abbott Laboratories,

720 F.3d 130 (Fed. Cir. 2013) .............. 12, 19, 23, 24

Statutes

28 U.S.C. § 1254(1) (2016)........................................... 2

28 U.S.C. § 1331 (2016) ............................................. 10

28 U.S.C. § 1338(a) (2016)......................................... 10

35 U.S.C. § 112 (2006) ....................................... passim

35 U.S.C. § 282 (2012) ....................................... passim

viii

INTRODUCTION

Since at least 1916, this Court has recognized that

a patent remains valid even if practicing the disclosed

invention requires some degree of experimentation.

An inventor may gain the monopoly granted by the

patent laws without performing the impossible task of

describing the precise embodiment that would be most

commercially successful in each case. To invalidate a

patent a challenger must do more than show that

practicing the patent, as disclosed, requires

experimentation; a challenger must show that

practicing

the

patent

requires

undue

experimentation.

This petition arises from the Federal Circuit’s

relaxation of the standard of proof required to show

that a patent is non-enabled under 35 U.S.C. § 112.

The patent statutes, this Court’s precedent, and

Federal Circuit precedent all unequivocally require a

patent challenger to demonstrate non-enablement by

clear and convincing evidence.

The Federal Circuit’s precedent in this case,

however, allows a challenger to invalidate a patent

that claims a class with particular functionality

without clear and convincing evidence of undue

experimentation. A challenger need only show that

the claimed class is large and that skilled artisans of

the time doubted the functionality of the invention. A

challenger need not proffer any evidence of

inoperability within the class. Without such evidence,

and relying instead only on mistaken disbelief in the

invention, it is impossible to draw any distinction

between permissible and undue experimentation

needed to practice an invention.

In applying such a lax standard, the Federal

Circuit’s precedential opinion contradicts a century of

its own and this Court’s precedent and contravenes

the standard of proof for proving patent invalidity. For

this reason, the Federal Circuit’s decision is improper

and warrants reversal.

OPINIONS BELOW

The district court’s opinions finding U.S. Patent

Nos. 6,992,180 (the “’180 patent”) and 8,097,405 (the

“’405 patent”) not enabled are unreported but

available at 2017 WL 2829625 and 2017 WL 3585618,

respectively, and reprinted at App. 19a–43a and 45a–

66a, respectively. The Federal Circuit affirmed the

district court judgment, as reported at 928 F.3d 1340

(2019) and reprinted at App. 1a–18a, and denied

rehearing in an order that is unreported but reprinted

at App. 67a–69a.

JURISDICTION

The Federal Circuit rendered its decision on June

20, 2019, App. 1a, and on October 29, 2019, denied

rehearing, App. 67a. On January 16, 2020, Chief

Justice Roberts granted application 19A800,

extending the time to file this petition to and including

February 26, 2020. This Court has jurisdiction

pursuant to 28 U.S.C. § 1254(1).

PERTINENT STATUTORY PROVISIONS

35 U.S.C. § 112 (2006) provides in relevant part:

Specification

The specification shall contain a written

description of the invention, and of the

manner and process of making and using it, in

such full, clear, concise, and exact terms as to

enable any person skilled in the art to which

it pertains, or with which it is most nearly

connected, to make and use the same.

35 U.S.C. § 282 provides in relevant part:

Presumption of validity; defenses

(a) In General.—

A patent shall be presumed valid. Each claim

of a patent (whether in independent,

dependent, or multiple dependent form) shall

be presumed valid independently of the

validity of other claims; dependent or multiple

dependent claims shall be presumed valid

even though dependent upon an invalid claim.

The burden of establishing invalidity of a

patent or any claim thereof shall rest on the

party asserting such invalidity.

STATEMENT OF THE CASE

At issue in this case is the standard of proof

necessary to establish a patent’s invalidity under 35

U.S.C. § 112. Under this Court’s precedent, invalidity

of a patent claim must be established by clear-andconvincing evidence. In the present case, however, the

Federal Circuit has allowed the Respondents to

invalidate the claims of two patents based merely on

mistaken notions of the art at the time of the

invention—without any evidence that members of the

class of nucleic acid probes claimed by the patents

would fail to exhibit the intended functionality. In so

doing, the Federal Circuit’s precedential opinion has

lowered the standard of proof to merely require

evidence that skilled artisans doubted the invention.

Background

A. Nucleic Acid Hybridization

Deoxyribonucleic acid (DNA) and ribonucleic acid

(RNA) are nucleic acids, which are comprised of linked

chains of nucleotides. Each nucleotide comprises three

parts: sugar, phosphate, and nitrogenous base. The

conventional nitrogenous bases in DNA are adenine,

guanine, cytosine, and thymine; in RNA, the

conventional bases are the same with the substitution

of uracil for thymine.

The nitrogenous bases of DNA and RNA bind

through non-covalent interactions in specific pairings

known as “Watson-Crick base pairs.” Adenine pairs

with—or is said to be complementary to—thymine or

uracil; guanine pairs with, or is complementary to,

cytosine. Two linked chains of nucleotides pair—or

hybridize—if the arrangement of nucleotides in each

strand results in sufficient Watson-Crick pairing of

the bases.

Nucleic acid hybridization enables scientists to

detect certain DNA or RNA sequences of interest.

Scientists can create a labeled oligonucleotide or

polynucleotide—i.e., a linked chain of nucleotides—

that contains a sufficiently complementary sequence

of bases to pair with, or hybridize to, the nucleic acid

of interest. The label, such as a fluorescent molecule

that emits a colored light, can be detected when the

oligonucleotide or polynucleotide hybridizes to a DNA

or RNA of interest, confirming the presence of the

sequence of interest. A labeled oligonucleotide or

polynucleotide that is both hybridizable and

detectable is called a probe.

B. The State Of The Art Before June 1982

Prior to the 1982 priority date of the ’180 and ’405

patents, nucleic acid hybridization was, in many

aspects, well understood. The structure of DNA and

RNA, the hybridization of nucleic acids via WatsonCrick base pairing, and creating and using

polynucleotide probes through radioactive labeling

were well developed within the field. Radioactive

labeling, however, involved replacing certain atoms in

the nucleotide sequence with radioactive isotopes and,

therefore, bore significant safety risks and costs,

engendering a need for non-radioactive methods.

The construction and use of non-radioactive

probes was a nascent field. In 1981, Dr. David Ward

demonstrated that non-radioactive labels could be

attached at specific base moieties (known as “Ward

positions”) to create probes. The prevailing—and

mistaken—perception in the art, however, was that

attaching non-radioactive labels anywhere on a

nucleic acid other than a Ward position would

compromise the hybridizability or detectability of the

intended probe.

Despite this misperception, skilled artisans of the

time understood a great deal of the science underlying

probes labeled non-radioactively at non-Ward

positions. For example, skilled artisans understood

how to construct a nucleic acid sufficiently

complementary to a target sequence and how to detect

various labels, such as detecting specific wavelengths

of light to locate a fluorescent label. Skilled artisans

also understood the chemistry—such as carbodiimide,

periodate oxidation, and alkylation chemistries—to

attach non-radioactive labels at non-Ward positions.

In other words, by June 1982, skilled artisans

could have created a non-radioactively, non-Ward

labeled probe and confirmed its functionality—if the

prevailing perception against its functionality had not

dissuaded them from so doing. The inventors of the

’180 and ’405 patents had the insight to see past that

mistaken perception.

C. The Inventions Of The ’180 And ’405

Patents

Against the prevailing dogma of the field,

scientists at Enzo conceived of making and using

probes labeled at phosphate and sugar moieties and

non-Ward positions of the base. The team conceived

that even polynucleotides labeled non-radioactively

at non-Ward positions can be sufficiently

complementary to hybridize and function as

detectable probes. That insight led to the patents.

The ’180 and ’405 patent specifications are, in

relevant part, identical. App. 4a. They identify the

structure of labeled nucleotides, as in “SIG-PM-SMBASE” or “PM-SM-BASE-Sig,” where SIG is a

signaling moiety, PM is a phosphate moiety, SM is a

sugar moiety, and BASE is a base moiety. The

specifications further explain that the inventions “are

useful for the tagging or labeling of DNA in a nondisruptive manner” and that a major utility of such

inventive polynucleotides is as “DNA or RNA probes”

that “contain one or more of the special Sig-containing

nucleotides.”

The asserted claims of the ’180 patent describe

phosphate-labeled probes—polynucleotides labeled at

the phosphate molecule that hybridize with

complementary nucleic acids and are detectable. The

invention of the ’180 patent is not directed to a specific

polynucleotide nor to a specific label nor method nor

location of labeling. The inventive insight of the ’180

patent was that polynucleotides with labels attached

to a phosphate would—contrary to mistaken notions

in the art at the time—function as a probe, i.e.,

hybridize and be detectable.

Claim 1, an independent claim from which

asserted claims depend, is exemplary:

1. An oligo- or polynucleotide which is

complementary to a nucleic acid of interest or

a portion thereof, said oligo- or polynucleotide

comprising at least one modified nucleotide or

modified nucleotide analog having the

formula:

Sig-PM-SM-BASE

wherein PM is a phosphate moiety, SM is a

furanosyl moiety and BASE is a base moiety

comprising a pyrimidine, a pyrimidine analog,

a purine, a purine analog, a deazapurine or a

deazapurine analog wherein said analog can

be attached to or coupled to or incorporated

into DNA or RNA wherein said analog does

not substantially interfere with double helix

formation or nucleic acid hybridization, said

PM being attached to SM, said BASE being

attached to SM and said Sig being covalently

attached to PM directly or through a nonnucleotidyl chemical linkage, and wherein

said Sig comprises a non-polypeptide, nonnucleotidyl, non-radioactive label moiety

which can be directly or indirectly detected

when attached to PM or when said modified

nucleotide is incorporated into said oligo- or

polynucleotide or when said oligo- or

polynucleotide is hybridized to said

complementary nucleic acid of interest or a

portion thereof, and wherein Sig comprises

biotin, iminobiotin, an electron dense

component, a magnetic component, a metalcontaining

component,

fluorescent

component, a chemiluminescent component, a

chromogenic component, a hapten or a

combination of any of the foregoing.

The asserted claims of the ’405 patent describe

two types of hybridization: in situ and liquid phase

hybridization. Like the invention of the ’180 patent,

the ’405 patent is directed to methods of using

polynucleotides that skilled artisans of the time

possessed the technical skills to employ, yet never did

so before the critical insight claimed in the patent:

that the claimed polynucleotides would work in the

claimed hybridization processes.

The in situ hybridization claims are directed to

using a probe labeled at non-Ward positions for in situ

hybridization

identify

and

enumerate

chromosomes. Independent claim 64 is exemplary.

The liquid phase hybridization claims of the ’405

patent describe using a non-radioactively labeled

polynucleotide as a probe in a novel process involving

hybridization and detection in a liquid medium. All

asserted liquid phase hybridization claims depend

from independent claim 189.

The specifications of both patents disclose

numerous examples of labels, linkages, and

chemistries to create the claimed probes and

hybridization

methods.

For

example,

the

specifications disclose labels comprising biotin,

iminobiotin, fluorescein, rhodamine, dansyl, haptens,

chromogenic compounds, iron oxide (magnetic),

ferritin (electron dense), and cobalt (metal

component). The specifications also provide examples

of chemical linkages, such as poly-L-lysine, 1,6diaminohexane, linkages comprising CH2NH, and

“olefin linkage arms.”

The inventors also provided examples of applying

known chemistry to create the claimed probes.

Example V discloses creating phosphate-labeled

polynucleotides for hybridization and detection by

using

carbodiimide

chemistry

couple

polybiotinylated

poly-L-lysine

biotinyl-1,6diaminohexane

phosphate

moieties

polynucleotides—both at the ends of the molecule and

internally. The specifications further disclose

attaching a label to numerous other non-Ward

positions on base moieties—e.g., the N3 position of a

pyrimidine; the C2, N3, and N7 positions of a purine;

and the N4 position of a cytosine using alkylation

chemistry—and that such labels are detectable when

the probes are hybridized. And the specifications

disclose using vicinal oxidation by periodate to attach

biotin to a polynucleotide, which results in the biotin

being attached to a sugar analog at the 3’ end of a

polynucleotide.

Thus, although the specific choices of nucleic acid

sequence, label, linker, and nucleotides to be labeled

were considered implementation details of the

inventions, the ’180 and ’405 patents disclosed

examples of each.

II. Prior Proceedings

A. District Court

This petition arises from four separate suits filed

in the United States District Court for the District of

Delaware. Enzo filed separate complaints against

Roche—i.e., Roche Molecular Systems, Inc., Roche

Diagnostics Corp., Roche Diagnostics Operations,

Inc., and Roche Nimblegen, Inc.—and BD—i.e.,

Becton Dickinson and Company, Becton Dickinson

Diagnostics Inc., and Geneohm Sciences, Inc.—for

infringement of the ’180 patent on January 30 and

March 6, 2012, respectively. And Enzo filed separate

complaints against Abbott—i.e., Abbott Laboratories

and Abbott Molecular, Inc.—for infringement of the

’180 and ’405 patents on March 6, 2012, and February

11, 2013, respectively. The district court had

jurisdiction over these actions pursuant to 28 U.S.C.

§§ 1331 and 1338(a).

On June 28, 2017, the district court ruled on two

motions for summary judgment of invalidity of the

’180 patent in the suits against Roche and BD: the

court denied summary judgment regarding written

description based on genuine disputes of material fact,

but granted summary judgment that the asserted

claims of the ’180 patent are invalid as non-enabled

under 35 U.S.C. § 112. App. 44a–66a.

Enzo agreed that the district court’s enablement

ruling on the ’180 patent would be deemed to apply to

the claims asserted against Abbott. On August 15,

2017, the district court denied a motion for summary

judgment of invalidity of the ’405 patent based on

written description, but the district court granted

summary judgment for Abbott that the asserted

claims of the ’405 patent are invalid as non-enabled

under 35 U.S.C. § 112. App. 19a–43a.

The district court entered final judgment of

invalidity in all suits.

B. Federal Circuit

Enzo timely appealed those judgments to the

Federal Circuit, which consolidated those appeals. As

phrased by the Federal Circuit, the relevant issue on

appeal was “whether [the specification] enables the

creation of a labeled probe that is both hybridizable

and detectable upon hybridization.” App. 10a. The

circuit court assumed that “the specification teaches

one of skill in the art how to create the broad range of

labeled polynucleotides covered by the claims,” but the

court concluded that “the specification fails to teach

one of skill in the art which combinations will produce

a polynucleotide that is hybridizable and detectable

upon hybridization.” Id.

Citing Wyeth & Cordis Corp. v. Abbott

Laboratories, 720 F.3d 130 (Fed. Cir. 2013) and In re

Wands, 858 F.2d 731 (Fed. Cir. 1988), the Federal

Circuit concluded that one of skill in the art would

need to engage in undue experimentation to identify

probes that possessed the desired functionality—i.e.,

were both hybridizable and detectable upon

hybridization. App. 11a-18a. The keystone of the

Federal Circuit decision was its finding of high

unpredictability in the art—a finding based upon

testimony that one skilled in the art would not have

believed, at the time, that the probes taught by the

patents would be hybridizable or detectable as probes.

App. 15a–16a. That belief, however, was mistaken

and, without any evidence of inoperable probes within

the claimed class, that belief was immaterial to

whether particular probes would hybridize or be

detectable. That belief was inconclusive as to the

amount of experimentation necessary to practice the

claims.

The circuit court affirmed the district court’s

summary judgment that the ’180 and ’405 patents

were not enabled, and the court denied Enzo’s timely

petition for a panel rehearing or rehearing en banc.

App. 67a–69a.

REASONS FOR GRANTING THE PETITION

I. The Federal Circuit’s Invalidation Of The

Patents Without Evidence Of Inoperable

Members Of The Claimed Classes

Undermines The Statutory Burden And

Standard Of Proof For Challenges To Patent

Validity.

A. To Show That A Patent Is Invalid, A

Challenger Must Meet A Clear And

Convincing Standard Of Proof.

A patent, once issued by the USPTO, “shall be

presumed valid,” and “[t]he burden of establishing

invalidity of a patent or any claim thereof shall rest

on the party asserting such invalidity.” 35 U.S.C.

§ 282. “Thus, by its express terms, § 282 establishes a

presumption of patent validity, and it provides that a

challenger must overcome that presumption to prevail

on an invalidity defense.” Microsoft Corp. v. i4i Ltd.,

564 U.S. 91, 100 (2011).

Although the statute “includes no express

articulation of the standard of proof” the party

asserting invalidity must meet, both this Court and

the Federal Circuit have concluded that § 282

establishes “‘a heavy burden of persuasion,’ requiring

proof of the defense by clear and convincing evidence.”

Id. at 100, 102; see also, e.g., Atlas Powder Co. v. E.I.

du Pont De Nemours & Co., 750 F.2d 1569, 1573 (Fed.

Cir. 1984) (“Under 35 U.S.C. § 282, a patent is

presumed valid, and the one attacking validity has the

burden of proving invalidity by clear and convincing

evidence.”). In Microsoft Corp. v. i4i Ltd., this Court

rejected a challenge to the clear and convincing

standard of proof required by § 282, noting that

“[f]or nearly 30 years, the Federal Circuit has

interpreted § 282 as we do today. During this

period, Congress has often amended § 282,

see, e.g., Pub. L. 104–141, § 2, 109 Stat. 352;

Pub. L. 98–417, § 203, 98 Stat. 1603; not once,

so far as we . . . are aware, has it even

considered a proposal to lower the standard of

proof. . . . Indeed, Congress has left the

Federal Circuit’s interpretation of § 282 in

place despite ongoing criticism, both from

within the Federal Government and without.”

564 U.S. at 113.

Since this Court’s 2011 decision in Microsoft

Corp., the Federal Circuit has continued to apply the

clear and convincing standard to invalidity

challenges—including those brought under the

enablement requirement of 35 U.S.C. § 112. See, e.g.,

Allergan, Inc. v. Sandoz Inc., 796 F.3d 1293, 1303

(Fed. Cir. 2015) (“[P]atents are presumed to be valid

and overcoming that presumption requires clear and

convincing evidence.”) (citing 35 U.S.C. §

282; Microsoft Corp., 564 U.S. at 113); Alcon Research

Ltd. v. Barr Labs., Inc., 745 F.3d 1180, 1188 (Fed. Cir.

2014) (“[P]atents are presumed to be valid and

overcoming this presumption requires clear and

convincing evidence.”) (citing 35 U.S.C. §

282; Microsoft Corp., 564 U.S. at 113). The Federal

Circuit purported to apply a clear and convincing

standard of proof to this case as well. See App. 9a.

The Federal Circuit Applies An “Undue

Experimentation” Test To Patent

Validity Challenges Under The

Enablement Requirement Of § 112.

Section 112 of the patent statute describes what

must be contained in a patent specification. Among

other requirements, the specification must contain “a

written description of the invention, and of the

manner and process of making and using it . . . [such]

as to enable any person skilled in the art to which it

pertains, . . . to make and use the same.” 35 U.S.C.

§ 112, ¶ 1 (2006). Thus, an applicant must describe

the claimed invention adequately and provide

sufficient description to enable the invention’s

production and use.

Under current Federal Circuit law, a party

challenging a patent’s validity under the enablement

requirement of § 112 “must show by clear and

convincing evidence that a person of ordinary skill in

the art would not be able to practice the claimed

invention without ‘undue experimentation.’” Allergan,

Inc., 796 F.3d at 1309 (quoting In re Wands, 858 F.2d

731, 736–37 (Fed. Cir. 1988)); Alcon Research Ltd.,

745 F.3d at 1188.

For at least fifty years, the Federal Circuit (and

its predecessor) has applied some variant of this

inquiry and, critically, has repeatedly emphasized

that necessary experimentation does not invalidate a

patent unless such experimentation sums to an undue

amount. See, e.g., Application of Eltgroth, 419 F.2d

918, 921 (C.C.P.A. 1970) (“[S]ome experimentation,

provided it is not an undue amount, is permissible.”).

“[A] disclosure complies with the how-to-make

requirement of 35 U.S.C. § 112 even though ‘some

experimentation, provided it is not an undue amount’

(and provided that it does not require ingenuity

beyond that to be expected of one of ordinary skill in

the art), is still required to adapt the invention to

particular settings.” Fields v. Conover, 443 F.2d 1386,

1390–91 (C.C.P.A. 1971) (internal citations omitted).

“Assuming some experimentation were needed, a

patent is not invalid because of a need for

experimentation. A patent is invalid only when those

skilled in the art are required to engage

in undue experimentation to practice the invention.”

W.L. Gore & Assocs., Inc. v. Garlock, Inc., 721 F.2d

1540, 1557 (Fed. Cir. 1983). “That some

experimentation is necessary does not preclude

enablement; the amount of experimentation, however,

must not be unduly extensive.” Atlas Powder Co., 750

F.2d at 1576.

In short, “[s]ome ‘trial and error’” to practice

claims does not invalidate a patent. W.L. Gore &

Assocs., 721 F.2d at 1557. The standard allows

experimentation to encourage inventors to disclose

their inventions; otherwise, to require a patent with

claims that cover a class or combinations, or other

groups with numerous embodiments, to elucidate

every possible embodiment without imposing any

experimentation on a practitioner would impose a

prohibitive burden of disclosure on inventors and

undermine the inventor’s ability to claim the full scope

of their invention. As the Federal Circuit’s

predecessor noted, “such a requirement would force an

inventor seeking adequate patent protection to carry

out a prohibitive number of actual experiments. This

would tend to discourage inventors from filing patent

applications in an unpredictable area since the patent

claims would have to be limited to those embodiments

which are expressly disclosed. A potential infringer

could readily avoid ‘literal’ infringement of such

claims by merely finding another analogous catalyst

complex.” Application of Angstadt, 537 F.2d 498, 502–

03 (C.C.P.A. 1976).

This Court recognized the same considerations

over a century ago in rejecting a challenge to a

patent’s validity on the argument that some testing

would be required to practice the full scope of the

claims:

Equally untenable is the claim that the patent

is invalid for the reason that the evidence

shows that when different ores are treated

preliminary tests must be made to determine

the amount of oil and the extent of agitation

necessary in order to obtain the best results.

Such variation of treatment must be within

the scope of the claims, and the certainty

which the law requires in patents is not

greater than is reasonable, having regard to

their subject matter. The composition of ores

varies infinitely, each one presenting its

special problem, and it is obviously impossible

to specify in a patent the precise treatment

which would be most successful and

economical in each case. The process is one for

dealing with a large class of substances and

the range of treatment within the terms of the

claims, while leaving something to the skill of

persons applying the invention, is clearly

sufficiently definite to guide those skilled in

the art to its successful application, as the

evidence abundantly shows. This satisfies the

law.

Minerals Separation v. Hyde, 242 U.S. 261, 270–71

(1916).1 It is to this Court’s reasoning in Minerals

Separation v. Hyde that Federal Circuit decisions

allowing some, but not undue, experimentation may

be traced. See, e.g., In re Wands, 858 F.2d at 737 n.19

(citing Minerals Separation, 242 U.S. at 270–71); W.L.

Gore & Assocs., Inc., 721 F.2d at 1557 (citing Minerals

Separation, 242 U.S. at 270–71).

Thus, under this Court’s and the Federal Circuit’s

longstanding precedent, an issued patent cannot be

found invalid without a showing—by clear and

convincing evidence—that any experimentation

necessary to practice the invention constitutes an

undue amount.

C. The Federal Circuit Applies An EightFactor Factual Test To Evaluate The

Degree Of Experimentation.

As to determining what constitutes an “undue

amount,” since 1988, the Federal Circuit has applied

a multi-factor test “in determining whether a

disclosure would require undue experimentation.” In

re Wands, 858 F.2d at 737. “After the challenger has

put forward evidence that some experimentation is

needed to practice the patented claim, the factors set

This Court’s precedent prior to Hyde required patents to

sufficiently disclose claimed inventions such that skilled artisans

were not forced to experiment to practice the claims. See, e.g.,

Consol. Elec. Light Co. v. McKeesport Light Co., 159 U.S. 465, 475

(1895); Howard v. Detroit Stove Works, 150 U.S. 164, 167 (1893);

Bene v. Jeantet, 129 U.S. 683, 685–86 (1889).

forth in Wands then provide the factual

considerations that a court may consider when

determining whether the amount of that

experimentation is either ‘undue’ or sufficiently

routine such that an ordinarily skilled artisan would

reasonably be expected to carry it out.” Alcon Research

Ltd., 745 F.3d at 1188.

The eight factors are “(1) the quantity of

experimentation necessary, (2) the amount of

direction or guidance presented, (3) the presence or

absence of working examples, (4) the nature of the

invention, (5) the state of the prior art, (6) the relative

skill of those in the art, (7) the predictability or

unpredictability of the art, and (8) the breadth of the

claims.” In re Wands, 858 F.2d at 737. “Enablement is

a question of law based on underlying facts.” Wyeth &

Cordis Corp. v. Abbott Labs., 720 F.3d 1380, 1384

(Fed. Cir. 2013).

D. In The Present Case, The Predictability

Of The Art Controlled The Federal

Circuit’s Analysis Of The Wands Factors,

Despite A Lack Of Evidence Of

Inoperable Embodiments Within The

Claimed Class.

In the present case, the Federal Circuit, reviewing

the district court’s summary judgment decisions de

novo, App. 8a–9a, applied the Wands factors and

found undue experimentation necessary to practice

the full scope of the asserted claims of both patents.

App. 10a–18a. The circuit panel did not, however,

consider all of the Wands factors; its opinion, which

focused on the ’180 patent,2 discusses only four: the

guidance and examples disclosed by the patent; the

skill of those in the art; the breadth of the claims;

and—the lynchpin of its analysis—the predictability

of the art. Id.

It is plain from the refrains throughout the panel’s

opinion that finding the art unpredictable determined

the panel’s finding on the three additional Wands

factors discussed. “Given the unpredictability of the

art at the time,” the circuit court found the guidance

in the specification to be insufficient. App. 12a–13a.

“[I]n light of the unpredictability in the art,” the

circuit court also found Example V to be an

insufficient working example. App. 13a–15a. “Given

such unpredictability in the art,” the court further

found the breadth of the claims “particularly

concerning.” App. 16a–17a. The predictability of the

art controlled the decision. This matters.

The finding of unpredictability in the art hung on

scant evidence. The ’180 patent claims phosphatelabeled polynucleotides that function as probes—i.e.,

are hybridizable and detectable. The evidence of

unpredictability in the art cited by the Federal Circuit

merely demonstrates a disbelief of the claimed

invention as a whole. It does not demonstrate a

The substantive analysis of the Federal Circuit’s opinion

focuses upon the ’180 patent. See App. 9a–18a. Upon finding the

asserted claims of the ’180 patent non-enabled, the circuit court

summarily extended its reasoning to the asserted claims of the

’405 patent on the rational that “[t]hose claims are broader than

the asserted claims of the ’180 patent.” App. at 18a. Accordingly,

the discussions of the Federal Circuit’s reasoning throughout

this petition are also focused upon the ’180 patent but warrant

reversal of the Federal Circuit’s decision as to both patents.

persistent inability of skilled artisans to distinguish

between operable or inoperable embodiments within

the claimed class. Indeed, it does not demonstrate

anything whatsoever about the frequency—or even

existence—of inoperable embodiments. Skilled

artisans simply did not believe that phosphate-labeled

polynucleotides would function as probes.

The Federal Circuit judgment rests on a few

snippets of testimony of two Enzo experts and one

inventor. Dr. Backman testified that “it was

commonly thought” that labels at non-Ward positions

“would interfere with or disrupt the hybridization

process.” App. 16a. This testimony does not indicate

whether labels at non-Ward positions would, in fact,

interfere with hybridization. The panel also cited coinventor Dr. Rabbani’s testimony that the inventors’

more aggressive modification of the nucleic acid was

considered “breaking the dogma.” App. 15a–16a. And

Dr. Sherman testified that skilled artisans “would

have been dissuaded” from testing or using nonWard–labeled polynucleotides and would have had to

test a non-Ward–labeled probe—not “to predict

whether it would actually hybridize” insofar as testing

the functionality of each particular probe, but to

“assure against the prevailing wisdom that [the

invention] could work.” App. 16a.

None of that testimony indicates how much

experimentation would be necessary to change the

mistaken perception that the invention would not

function as claimed. That disbelief may have been

resolved by a single, “aha!” experiment.

Nor does that testimony indicate whether skilled

artisans—once dispelled of the mistaken belief that

phosphate-labeled

polynucleotides

would

not

hybridize and be detectable—would be able to

distinguish between those polynucleotides that would

or would not function as probes. Critically, the

defendants below presented no evidence of inoperable

members within the claimed class. Although the

Federal Circuit notes that the claims may encompass

“tens of thousands” of possible embodiments, App.

17a, nowhere does the circuit opinion address whether

even one of those thousands would fail to function as

claimed.

Without evidence of inoperable embodiments

within the class of phosphate-labeled probes claimed

by the ’180 patent, it is as likely that all claimed

phosphate-labeled polynucleotides would hybridize

and be detectable as it is that only some would exhibit

the intended functionality. Without evidence favoring

either scenario, the line between routine and undue

experimentation cannot be drawn.

Nonetheless, the Federal Circuit incorrectly or

erroneously assumed that some embodiments would

not function as desired and, therefore, found the

asserted claims of both the ’180 and ’405 patents

invalid: “[E]ven if Example V describes one working

embodiment with the claimed functionality, undue

experimentation would still be required with regard

to the many other embodiments of the claims based on

the number of possible embodiments and the

unpredictability in the art.” App. 17a–18a.

E. The Federal Circuit’s Invalidation Of

Patent Claims Without Evidence Of

Inoperable Embodiments In The

Claimed Class Warrants Review And

Reversal.

The Federal Circuit’s precedential decision in this

case impermissibly lowers the clear and convincing

standard of proof for challengers seeking to invalidate

patents under 35 U.S.C. § 112 and impermissibly

shifts the burden to the patent owner to prove patent

claims are enabled, and therefore valid, in violation of

the presumption of validity and assignment of the

burden of proof under 35 U.S.C. § 282.

Prior to its decision in this case, the Federal

Circuit found claims covering a broad class invalid

under § 112 due to unpredictability of the art only

upon a showing that some members of the broad class

would not exhibit the claimed functionality. For

example, in Wyeth & Cordis Corp. v. Abbott

Laboratories, upon which the circuit panel in this case

relied, the Federal Circuit found claims covering a

class of compounds with immunosuppressive and

antirestinosis effects invalid due to the large number

of possible embodiments and unpredictability of the

art. 720 F.3d at 1382–83, 1385–86. But, unlike the

present case, the patent challenger had offered

testimony from the patent owner that “even minor

alterations to the . . . molecule could impact its

immunosuppressive and antirestinotic properties.” Id.

at 1384–85. In other words, rather than evidence that

skilled artisans did not believe in the claimed

invention, the challenger showed that not all

members of the class would exhibit the claimed

functionality: “you really can’t tell whether they work”

without “first synthesiz[ing] and then screen[ing] each

compound.” Id. at 1385. Because not all members

functioned as claimed, that experimentation would

necessarily continue for every member of the class.

By contrast, in Alcon Research Ltd. v. Barr

Laboratories, Inc., the Federal Circuit rejected a

challenge to broad claims. The district court had held

the claims invalid under In re Wands upon finding

that the claims were too broad and the art too

unpredictable. 745 F.3d at 1185. The evidence

included testimony that “many ‘variables’ . . .

including

pH,

buffer,

buffer

concentration,

preservatives, chelating agents, and other excipients

may affect the chemical stability” and testimony that

“when ‘you have a lot of variables on top of one

another, the experimentation gets out of control

quickly.’” Id. at 1189 (emphasis in original). The

Federal Circuit, however, reversed because no

evidence demonstrated whether “changing any of the

‘variables’ . . . would render Alcon’s claimed invention

inoperable.” Id. Without such evidence, conclusions

about the predictability of the art were

unsubstantiated and “not sufficient” to show “any

experimentation, let alone undue experimentation.”

Id. at 1189–90.

More recently, the Federal Circuit decided Idenix

Pharmaceuticals LLC v. Gilead Sciences, Inc. on

similar grounds as in Wyeth. 941 F.3d 1149 (Fed. Cir.

2019). The asserted patent claimed methods for

treating the Hepatitis C virus (“HVC”). Id. at 1154–

55. In evaluating the evidence under the Wands

factors, the Federal Circuit found the number of

compounds encompassed by the claims to number “at

least many, many thousands.” Id. at 1157. And the

court found the art highly unpredictable, both because

the field was “in its infancy”—similar to the present

case—and due to testimony that “not all 2’ methyl up

ribonucleosides will be effective to treat HCV”—

evidence lacking in the present case—and “you don’t

know whether or not a nucleoside will have activity

against HCV until you make and test it.” Id. at 1159,

1161.

In sum, under these Federal Circuit decisions, a

patent challenger must show that not all

embodiments within a class exhibit the claimed

functionality. Such evidence, combined with evidence

of a broad class covered by the claims, could support a

conclusion of undue experimentation under the

Wands factors and, in turn, support a judgment of

patent invalidity under § 112.

The precedential decision in the present case,

however, lowers the evidentiary burden. Under the

precedent set by this case, a patent challenger need

only demonstrate that the claims cover a large class

and that skilled artisans of the time doubted the

functionality of the invention. Without evidence that

some members of the claimed class would not exhibit

the desired functionality, such doubt fails to

meaningfully inform any analysis of experimentation

necessary to practice a patent. The evidence does not

demonstrate how much experimentation would be

necessary to dispel such doubt. Under this precedent,

any experimentation necessary to dispel doubt and

confirm the functionality of patent claims may be

presumed to be undue experimentation.

Such a result contravenes this Court’s conclusion

in Microsoft Corp. v. i4i Ltd. that, under § 282, patent

challengers must meet the “heavy burden of

persuasion” of the “clear and convincing” standard of

proof. 564 U.S. at 100. Allowing a lower standard of

proof to comply—even within the subset of patents

over which this precedential opinion will be

relevant—undermines the quid pro quo of the patent

system. The heightened standard of proof is an

essential component of the patent “bargain” and the

incentives for inventors to disclose their innovations

to the public in exchange for patent protection. See

Bonito Boats, Inc. v. Thunder Craft Boats, Inc., 489

U.S. 141, 150–51 (1989).

Indeed, by allowing patent challengers to

establish undue experimentation based merely on a

mistaken dogma present in the art—without any

evidence of substantial experimentation necessary to

overcome that mistaken belief—the Federal Circuit’s

precedential decision in this case effectively and

improperly shifts the burden onto the patentee to

demonstrate that such disbelief could be dispelled

through routine experimentation. The patentee would

be tasked with proving the operability of every

member of a claimed class, despite an absence of

evidence that a skilled artisan would encounter any

inoperable members of the claimed class, let alone

such a significant number of inoperable members that

the artisan would have had to engage in an unduly

extensive trial-and-error process to practice the

claims. Nearly 150 years of this Court’s precedent

make clear that a patent-holder like Enzo is not

tasked with disproving doubts about the validity of its

duly issued patent: “As early as 1874 [this Court]

explained that the burden of proving [invalidity] ‘rests

upon [the defendant], and every reasonable doubt

should be resolved against him.’” Microsoft Corp., 564

U.S. at 105 (quoting Coffin v. Ogden, 85 U.S. 120, 124

(1873)); see also Minerals Separation v. Hyde, 242 U.S.

at 271 (“[I]t is obviously impossible to specify in a

patent the precise treatment which would be most

successful and economical in each case.”). Shifting the

burden, as the Federal Circuit has done in this

precedential case, violates the plain language of § 282

that “[t]he burden of establishing invalidity of a

patent or any claim thereof shall rest on the party

asserting such invalidity.” 35 U.S.C. § 282.

CONCLUSION

For the foregoing reasons, the petition for a writ

of certiorari should be granted.

Respectfully submitted.

JOHN M. DESMARAIS

JUSTIN P.D. WILCOX,

Counsel of Record

DESMARAIS LLP

230 Park Avenue

New York, NY 10169

(212) 351-3400

jdesmarais@desmaraisllp.com

jwilcox@desmaraisllp.com

PETER C. MAGIC

DESMARAIS LLP

101 California Street

San Francisco, CA 94111

(415) 573-1900

pmagic@desmaraisllp.com

Counsel for Petitioner

Enzo Life Sciences, Inc.

APPENDIX

Appendix A — Appendix

opinionAof the United

States Court of Appeals for the

Federal Circuit, FILED JUNE 20, 2019

United States Court of Appeals

for the Federal Circuit

ENZO LIFE SCIENCES, INC.,

Plaintiff-Appellant

ROCHE MOLECULAR SYSTEMS, INC., ROCHE

DIAGNOSTICS CORPORATION, ROCHE

DIAGNOSTICS OPERATIONS, INC., ROCHE

NIMBLEGEN, INC., BECTON, DICKINSON

AND COMPANY, AKA BECTON DICKSON AND

COMPANY, BECTON DICKINSON DIAGNOSTICS

INC., AKA BECTON DICKSON DIAGNOSTICS,

GENEOHM SCIENCES INC., ABBOTT

LABORATORIES, ABBOTT MOLECULAR, INC.,

Defendants-Appellees

2017-2498, 2017-2499, 2017-2545, 2017-2546

Appeals from the United States District Court for the

District of Delaware in Nos. 1:12-cv-00106-LPS, 1:12-cv00274-LPS, 1:12-cv-00275-LPS, 1:13-cv-00225-LPS, Chief

Judge Leonard P. Stark.

*This opinion was originally filed under seal and has been

unsealed in full.

Appendix A

June 20, 2019, Sealed Opinion Issued;

July 5, 2019*, Public Opinion Issued

Before PROST, Chief Judge, REYNA and WALLACH,

Circuit Judges.

PROST, Chief Judge.

Enzo Life Sciences, Inc. (“Enzo”) appeals the decision

of the U.S. District Court for the District of Delaware

granting summary judgment against Enzo and holding

that the asserted claims are invalid for lack of enablement.

We affirm as to non-enablement and do not reach the other

issues presented on appeal.

Deoxyribonucleic acid (“DNA”) and ribonucleic acid

(“RNA”) are nucleic acids. They are made of a series

of building blocks, called nucleotides, linked together

in a chain. A single nucleotide is made up of a sugar, a

phosphate, and a nitrogenous base. DNA nucleotides have

one of four nitrogenous bases: adenine (A); guanine (G);

cytosine (C); and thymine (T). RNA has the same bases,

except it uses uracil (U) instead of thymine (T).

A polynucleotide refers to multiple nucleotides linked

together in a chain.1 The nucleotides located at each end

of a polynucleotide chain are referred to as terminal

1. An oligonucleotide is simply a shorter polynucleotide (e.g.,

just a few nucleotides in length).

Appendix A

nucleotides. All other nucleotides in a polynucleotide chain

are referred to as internal nucleotides.

Two strands of polynucleotides can pair with each

other, i.e., hybridize, through hydrogen bonding between

the bases on each polynucleotide strand. The bases T and

U pair with A, while G pairs with C. This is referred to

as complementary base pairing or “Watson-Crick base

pairing,” and this pairing is how the now-familiar double

helix shape is formed. Two polynucleotide strands will

hybridize if the arrangement of nucleotides in each strand

is such that enough bases can pair with each other. For

example, whether two strands will hybridize depends in

part on the number of complementary base pairs that

exist between the two polynucleotides.

Hybridization techniques are used to detect the

presence of certain nucleic acid sequences of interest,

i.e., target sequences, such as genetic alterations. In such

procedures, scientists use a hybridization “probe”—i.e.,

a labeled polynucleotide that is hybridizable and remains

detectable after hybridization occurs—that is sufficiently

complementary to the target sequence. The probe will

hybridize with the target sequence if the target sequence

is present, and the label on the probe then allows scientists

to detect the hybridized probe.

Nucleic acid hybridization was well understood by

June 1982, which is the claimed priority date of the

patents at issue in this appeal. The prevailing method of

labeling probes at that time was via radioactive labeling.

Radioactive labeling generally involved replacing certain

Appendix A

atoms in the nucleotide sequence with corresponding

radioactive isotopes.

Non-radioactive labeling was just developing at the

time of the claimed inventions. In 1981, Dr. David Ward

and others at Yale University successfully developed

a nonradioactive probe by attaching a label to a

polynucleotide via a chemical linker at a base position of

a nucleotide. See J.A. 4129-33 (publication by Dr. Ward

and others titled “Enzymatic synthesis of biotin-labeled

polynucleotides: Novel nucleic acid affinity probes”).

Dr. Ward demonstrated that attaching labels at certain

positions of the nucleotide (“the Ward positions”) would

not disrupt the polynucleotide’s ability to hybridize and

be detected upon hybridization.

In December 1981, Enzo licensed the exclusive rights

to the patent portfolio covering Dr. Ward’s discovery. See

J.A. 4258-75. Shortly thereafter, in June 1982, Enzo filed

a patent application covering non-radioactive labeling at

additional positions on a nucleotide. The two patents in

this appeal issued from applications filed in 1995 that claim

priority from this 1982 application.

Both patents in this appeal generally relate to the use

of non-radioactively labeled polynucleotides in nucleic acid

hybridization and detection applications. The patents share

the same specification in relevant part. See J.A. 90 n.6.

U.S. Patent No. 6,992,180 (“the ’180 patent”) relates

to non-radioactive labeling of polynucleotides where the

Appendix A

label is attached at the phosphate position of a nucleotide.

The claims are not directed to any specific polynucleotide,

nor do they focus on the chemistry or linker used to attach

a label, the number of labels to attach to a polynucleotide,

or where within the polynucleotide to attach those labels.

Instead, the claims encompass all polynucleotides with

labels attached to a phosphate, as long as the polynucleotide

remains hybridizable and detectable upon hybridization.

Claim 1 of the ’180 patent is representative:

1. A n oligo - or poly nucleotide which is

complementary to a nucleic acid of interest or

a portion thereof, said oligo- or polynucleotide

comprising at least one modified nucleotide or

modified nucleotide analog having the formula

Sig-PM-SM-BASE

wherein PM is a phosphate moiety, SM is a

furanosyl moiety and BASE is a base moiety

comprising a pyrimidine, a pyrimidine analog,

a purine, a purine analog, a deazapurine or a

deazapurine analog wherein said analog can

be attached to or coupled to or incorporated

into DNA or RNA wherein said analog does

not substantially interfere with double helix

formation or nucleic acid hybridization,

said PM being attached to SM, said BASE

being attached to SM, and said Sig being

covalently attached to PM directly or through

a non-nucleotidyl chemical linkage, and

wherein said Sig comprises a non-polypeptide,

non-nucleot idyl, non-radioactive label

Appendix A

moiety which can be directly or indirectly

detected when attached to PM or when

said modified nucleotide is incorporated

into said oligo- or polynucleotide or when

said oligo- or polynucleotide is hybridized

to said complementary nucleic acid of

interest or a portion thereof, and wherein Sig

comprises biotin, iminobiotin, an electron dense

component, a magnetic component, a metalcontaining component, a fluorescent component,

a chemiluminescent component, a chromogenic

component, a hapten or a combination of any of

the foregoing.

’180 patent claim 1 (emphases added).

“Sig” represents a signaling moiety (i.e., a label); PM

represents a phosphate moiety; SM represents a sugar

moiety; and BASE represents a base moiety.

The asserted claims of U.S. Patent No. 8,097,405

(“the ’405 patent”) fall into two categories: (1) in situ

hybridization claims; and (2) liquid phase hybridization

claims.

The in situ hybridization claims (claims 63, 64, 65, 95,

103, 128, and 144) describe a process that uses a probe nonradioactively labeled at any non-Ward position to identify

chromosomes. In situ hybridization is where probes are

hybridized to a target that is fixed, usually on a glass slide.

Claim 64 is exemplary.

Appendix A

The liquid phase hybridization claims (claims 196

and 198) describe a process that uses a non-radioactively

labeled probe to hybridize and detect a target sequence

in a liquid medium, rather than on a glass slide. These

claims cover using probes labeled non-radioactively at

any position on the nucleotide, including the three Ward

positions. The asserted liquid phase hybridization claims

depend from claim 189.

This consolidated appeal involves four district court

cases. 2 The ’180 patent is at issue in all four cases, while

the ’405 patent is at issue only in the cases against Abbott.

In January 2012, Enzo filed suit against Roche

Molecular Systems, Inc., Roche Diagnostics Corp., Roche

Diagnostics Operations, Inc., and Roche Nimblegen, Inc.

(collectively, “Roche”) alleging infringement of the ’180

patent. J.A. 1212-16 (Compl.) (Case No. 1:12-cv-106). In

March 2012, Enzo filed separate suits against Becton,

Dickinson and Co., Becton Dickinson Diagnostics Inc., and

GeneOhm Sciences, Inc. (collectively, “BD”); and Abbott

Laboratories and Abbott Molecular, Inc. (collectively,

“Abbott”) alleging infringement of the ’180 patent. J.A.

2833-36 (Compl.) (Case No. 1:12-cv-275 against BD); J.A.

1964-67 (Compl.) (Case No. 1:12-cv-274 against Abbott).

In February 2013, Enzo filed a second suit against Abbott

alleging infringement of the ’405 patent. J.A. 3973-77

(Compl.) (Case No. 1:13-cv-225).

2. Appeal Nos. 17-2354 and 17-2355 were dismissed by

agreement of the parties in those appeals. ECF No. 98.

Appendix A

In June 2017, in the cases against Roche and BD, the

district court denied summary judgment with respect to

written description, but granted summary judgment in

favor of the defendants, holding that all asserted claims of

the ’180 patent were invalid as not enabled. See J.A. 59-77,

99-117. The district court entered partial final judgment

of invalidity pursuant to Federal Rule of Civil Procedure

54(b) with respect to the claims of the ’180 patent in the

cases against BD and Roche. J.A. 14-18 (BD), 5-9 (Roche).

In the two Abbott cases, Enzo agreed that the district

court’s earlier enablement ruling as to the ’180 patent

would be deemed to apply to the claims of that patent

asserted against Abbott. J.A. 23, 14950-51. As to the ’405

patent, in August 2017, the district court denied Abbott’s

motion as to written description but granted summary

judgment in favor of Abbott, holding the claims invalid for

lack of enablement. J.A. 78-98. The district court entered

final judgment of invalidity of all asserted claims of the

’180 and ’405 patents on September 1, 2017. J.A. 10-13,

23-26.

Enzo timely appealed each judgment. This court

consolidated the appeals. We have jurisdiction under 28

U.S.C. § 1295(a)(1).

In reviewing a grant of summary judgment, we apply

the law of the regional circuit. Vasudevan Software, Inc. v.

MicroStrategy, Inc., 782 F.3d 671, 676 (Fed. Cir. 2015). The

Third Circuit reviews a district court’s grant of summary

Appendix A

judgment de novo. Melrose, Inc. v. City of Pittsburgh,

613 F.3d 380, 387 (3d Cir. 2010). “Summary judgment is

appropriate only where, drawing all reasonable inferences

in favor of the nonmoving party, there is no genuine

issue as to any material fact and . . . the moving party

is entitled to judgment as a matter of law.” Id. (quoting

Ruehl v. Viacom, Inc., 500 F.3d 375, 380 n.6 (3d Cir. 2007)).

“[U]nless there is sufficient evidence favoring the

nonmoving party for a jury to return a verdict for that

party,” there is no need for a trial, and summary judgment

is appropriate. Anderson v. Liberty Lobby, Inc., 477 U.S.

242, 249, 106 S. Ct. 2505, 91 L. Ed. 2d 202 (1986).

III

The enablement requirement asks whether “the

specification teach[es] those in the art to make and use

the invention without undue experimentation.” In re

Wands, 858 F.2d 731, 737 (Fed. Cir. 1988). To satisfy this

requirement, “[t]he specification must contain sufficient

disclosure to enable an ordinarily skilled artisan to

make and use the entire scope of the claimed invention

at the time of filing.” MagSil Corp. v. Hitachi Glob.

Storage Techs., Inc., 687 F.3d 1377, 1381 (Fed. Cir. 2012).

“Enablement is a question of law based on underlying

factual findings.” Id. at 1380.

“To prove that a claim is invalid for lack of enablement,

a challenger must show by clear and convincing evidence

that a person of ordinary skill in the art would not be

able to practice the claimed invention without ‘undue

experimentation.’” Alcon Research Ltd. v. Barr Labs.,

10a

Appendix A

Inc., 745 F.3d 1180, 1188 (Fed. Cir. 2014) (quoting In

re Wands, 858 F.2d at 736-37). 3 In analyzing undue

experimentation, we consider factors such as: “(1) the

quantity of experimentation necessary, (2) the amount

of direction or guidance presented, (3) the presence

or absence of working examples, (4) the nature of the

invention, (5) the state of the prior art, (6) the relative skill

of those in the art, (7) the predictability or unpredictability

of the art, and (8) the breadth of the claims.” In re Wands,

858 F.2d at 737.

In our view, the issue in this appeal is not simply

whether the specification enables labeling; the question

is whether it enables creation of a labeled probe that is

both hybridizable and detectable upon hybridization.

Many of the alleged factual disputes raised by Enzo and

many of the arguments raised by Appellees relate to

the details of creating the labeled polynucleotide. For

example, Roche and BD contend that the specification

fails to sufficiently disclose internal phosphate labeling.

But even if we assume that the specification teaches one

of skill in the art how to create the broad range of labeled

polynucleotides covered by the claims, as explained below,

the specification still fails to teach one of skill in the art

which combinations will produce a polynucleotide that

is hybridizable and detectable upon hybridization, as

required by the claim language.

3. In this case, the parties agree that the relevant person of

ordinary skill in the art is a scientist with a doctorate in chemistry,

biochemistry, biophysics, molecular biology, or a similar field.

Appellant’s Br. 30 (noting the parties’ agreement).

11a

Appendix A

With this focus on the functionality required by

the claims, we agree with Appellees that our decision

in Wyeth and Cordis Corp. v. Abbott Laboratories, 720

F.3d 1380 (Fed. Cir. 2013), controls this case. In Wyeth,

we affirmed a grant of summary judgment and held the

asserted claims invalid for lack of enablement because it

would have required undue experimentation to determine

which compounds in the claimed class would have the

required functionality. Id. at 1385-86. The claims in

Wyeth were construed to require a compound having

certain functionality (e.g., immunosuppressive effects).

Id. at 1383. The claims covered a class of compounds

that met those functional requirements. Id. at 1385. The

patentee’s witnesses testified that minor alterations to the

molecule disclosed in the specification could impact the

required functionality. Id. The patent challengers in that

case thus argued that a person of ordinary skill in the art

would need to screen each compound to determine what

candidates would have the claimed functionality. Id. We

agreed. Id. We noted the breadth of the claims, the limited

guidance provided in the specification, the large number of

possible candidates falling within the claimed genus (tens

of thousands), and the fact that it would be necessary to

first synthesize and then screen each of those candidates

to determine whether it had the required functionality.

Id. We further noted that one of the patentee’s scientists

had confirmed the unpredictability in the art by testifying

that one would need to test each compound to understand

whether it would have the desired functionality. Id. We

thus concluded that there was no genuine dispute that

practicing the full scope of the claims would require undue

experimentation. Id.

12a

Appendix A

The facts in this appeal largely mirror those in Wyeth.

As in Wyeth, the asserted claims here require not just a

particular structure, but a particular functionality (i.e.,

the labeled polynucleotides must be hybridizable and

detectable upon hybridization). As explained below, the

specification fails to teach one of skill in the art whether

the many embodiments of the broad claims would exhibit

that required functionality.

The scope of the claims is quite broad. Claim 1

of the ’180 patent encompasses all phosphate-labeled

polynucleotides that are hybridizable and detectable. The

claim places almost no limitations on the structure of the

claimed polynucleotide, other than the fact that the label

is attached to the phosphate portion of the nucleotide. It

does not restrict the chemistry used to attach the label, the

chemical linker used, the number of labels within a probe,

or the location of the labels on the probe (i.e., whether they

are terminal or internal). As to the type of non-radioactive

label used, the claim provides broad categories, such as

any “electron dense component” or “magnetic component.”

The specification’s guidance as to how such variables

would or would not impact the functionality of the

claimed probes is sparse. For example, Enzo directs our

attention to a sentence in the specification that states

that “[a] particularly important and useful aspect of the

special nucleotides of this invention is the use of such

nucleotides in the preparation of DNA or RNA probes.”

’180 patent col. 54 ll. 18-20; see also id. col. 54 ll. 18-33

(describing generally how a probe works). Enzo’s expert,

Dr. Backman, explained that a skilled artisan would have

understood this reference to using the polynucleotide as

13a

Appendix A

a “probe” as meaning a polynucleotide that is capable of

hybridizing and being detected upon hybridization. J.A.

5840-41 ¶ 57 (Backman Decl.). But at the time of the

invention, the art was highly unpredictable. As Enzo’s

expert explained:

At the time of the inventions of the ’180 patent,

it was commonly thought that the addition of a

non-radioactive label to a nucleic acid sequence

at positions other than a few known as ‘nondisruptive positions’ . . . would interfere with or

disrupt the hybridization process, rendering the

nucleotide ineffective for diagnostic purposes.

J.A. 4728 ¶ 74 (Backman Opening Report).

Given the unpredictability of the art at the time

and the serious doubts held by those of skill in the art

regarding whether labels could be attached to non-Ward

positions without disrupting hybridization, merely stating

that a labeled polynucleotide will work as a probe is not

sufficient to enable one of skill in the art to know that it

would indeed function as a probe—i.e., be hybridizable

and detectable upon hybridization.

Enzo also presents Example V as an example of

an internal phosphate-labeled polynucleotide that is

hybridizable and detectable. Appellant’s Br. 32-33.

Example V states in full:

Biotin and polybiotinylated poly-L-lysine

were coupled to oligoribonucleotides using a

14a

Appendix A

carbodiimide coupling procedure described

by Halbran and Parker, J. Immunol., 96 373

(1966). As an example, DNA (1 ug/ml), 1 ml)

in tris buffer pH 8.2, sheared with 0.1 N

sodium hydroxide was denatured by boiling

for 10 minutes and quick cooling in an ice bath.

Biotinyl-1,6-diaminohexane amide (2 mg, 6

umol) or polybiotinylated poly-L-lysine (2 mg)

and l-ethyl-3-diisopropylaminocarboimide

HCl (10 mg, 64 umol) were added, and the

pH readjusted to 8.2. After 24 hours at room

temperature in the dark, the mixture was

dialyzed against 10 mM tris buffered saline.

DNA was precipitated ethanol.

’180 patent col. 33 ll. 33-44.

Appellees contend that Example V is not a working

example. During prosecution, Enzo admitted that Example

V is a “’paper’, rather than [a] ‘working example[].’” J.A.

4703 (stating in an amendment made during prosecution

that “Applicants have determined that the examples set

forth . . . [except certain examples other than Example V]

are ‘paper’, rather than ‘working examples’”); J.A. 6657

(same). Additionally, Enzo’s expert testified that he was

not aware of Enzo having ever tested a phosphate-labeled

probe for hybridizability and detectability. J.A. 8547-48

p. 84 l. 5-p. 85 l. 16 (Backman deposition); J.A. 8551-52 p.

124 l. 10-p. 125 l. 11 (Backman deposition); see also J.A.

6441 p. 133 ll. 6-15 (Backman deposition) (“Q: . . . is there

any bench experiment disclosed in the ’180 patent in which

the ’180 inventors attempted to determine whether the

15a

Appendix A

product of Example V, that is, the Sig moiety attached to

an oligo- or polynucleotide could be detected after it had

hybridized to a compl[e]mentary nucleic acid of interest?

A. . . . no, they did not do an actual bench experiment to

that effect.”); id. p. 131 ll. 7-19. Regardless, even viewing

Example V as a working example, Example V is insufficient

to enable the breadth of the claims here, especially in light

of the unpredictability in the art.4

The deficiencies in the description as to enablement

cannot be cured in this case by looking to the knowledge

of those skilled in the art at the time of the invention.

Although “a specification need not disclose what is well

known in the art,” that rule is “not a substitute for a basic

enabling disclosure.” Genentech, Inc. v. Novo Nordisk

A/S, 108 F.3d 1361, 1366 (Fed. Cir. 1997). As we have said

before, a patentee “cannot simply rely on the knowledge of

a person of ordinary skill to serve as a substitute for the

missing information in the specification.” ALZA Corp. v.

Andrx Pharms., LLC, 603 F.3d 935, 941 (Fed. Cir. 2010).

And, more importantly, all parties acknowledge that

serious doubts existed in the art as to whether the use

of non-radioactive probes at non-Ward positions would

be useful as probes. For example, an inventor of the ’180

patent who is also Enzo’s CEO explained that, at the time,

it was thought “aggressive chemical modification of nucleic

4. Nothing stated herein would necessarily disallow proper

constructive examples, which are intended to fulfill both written

description and enablement requirements. Atlas Powder Co. v. E.I.

du Pont De Nemours & Co., 750 F.2d 1569, 1577 (Fed. Cir. 1984)

(“Use of prophetic examples, however, does not automatically make

a patent non-enabling.”).

16a

Appendix A

acid would lead to destruction of his [sic] content.” J.A.

6470 p. 1265 l. 5-p. 1266 l. 15 (Dr. Rabbani deposition); see

also J.A. 6465 p. 31 l. 12-p. 33 l. 13 (Dr. Rabbani explaining

how more aggressive modification of the nucleic acid

was considered “breaking the dogma”). Enzo’s expert,

Dr. Backman, also pointed out the view of the art at the

time, stating that “[a]t the time of the inventions of the

’180 patent, it was commonly thought that the addition

of a nonradioactive label to a nucleic acid sequence at

positions other than [the Ward positions at the base] would

interfere with or disrupt the hybridization process.” J.A.

4728 ¶ 74 (Backman’s Opening Report); J.A. 4184 ll. 10-24

(Dr. Rabbani deposition). Indeed, Enzo’s expert explained

that for one of skill in the art to be comfortable that a

particular polynucleotide would work as a probe, “they

would need to actually make the compound and test it in

a hybridization experiment, which they would have been

dissuaded from doing because of Ward.” J.A. 8454 p. 150

ll. 8-15 (Sherman deposition) (discussing a polynucleotide

labeled at the terminal phosphate and using carbodiimide

chemistry and biotin); see also J.A. 8456 ll. 3-11 (Sherman

deposition) (“Q: . . . But if they had been motivated to make

this probe, non-Ward labeled probe, your view is that

they would have to make it and test it in order to predict

whether it would actually hybridize as of June 1982, right?

A: Well, they would have to make it and assure against

the prevailing wisdom that it could work.”); J.A. 8454-55

p. 150 l. 17-p. 151 l. 18 (Sherman deposition).

Given such u npred ict abi l ity i n the a r t , a nd

considering the testimony of Enzo’s expert that each

labeled polynucleotide would need to be tested to

17a

Appendix A

determine whether it is hybridizable and detectable

upon hybridization, the breadth of the claims here is

particularly concerning in the enablement inquiry. See In

re Fisher, 427 F.2d 833, 839, 57 C.C.P.A. 1099 (CCPA 1970)

(“In cases involving unpredictable factors, such as most

chemical reactions and physiological activity, the scope

of enablement obviously varies inversely with the degree

of unpredictability of the factors involved.”). Appellees

contend that millions of embodiments of the claims exist

based on the many variables involved in creating one of

the claimed labeled polynucleotides. Enzo disputes this

number, arguing it is improperly inflated because it counts

every possible polynucleotide sequence that could exist as

a separate embodiment. Even assuming Enzo is correct

that the length and sequence of the polynucleotide do not

give rise to separate embodiments, the other variables

(such as the type of label, the type of linker used to

attach the label, and the location of the labels within the

polynucleotide) still result in an extremely large number

of possible embodiments. Indeed, Enzo’s expert explained

that the number of possible polynucleotides that would fit

within the limitations of claim 1 would be at least “tens of

thousands.” J.A. 6438 p. 120 l. 20-p. 121 l. 11 (Backman

deposition).

In sum, even if Example V describes one working

embodiment with the claimed functionality, undue

experimentation would still be required with regard to

the many other embodiments of the claims based on the

number of possible embodiments and the unpredictability

in the art. See Genentech, 108 F.3d at 1366 (“Patent

protection is granted in return for an enabling disclosure

18a

Appendix A

of an invention, not for vague intimations of general ideas

that may or may not be workable.”).

We conclude by briefly addressing the asserted claims

of the ’405 patent. Those claims are broader than the

asserted claims of the ’180 patent; rather than covering

only phosphate-labeled polynucleotides, they also cover

labeling at other locations on a nucleotide. Like the claims

of the ’180 patent, the asserted claims of the ’405 patent

require the claimed polynucleotides to be hybridizable and

detectable upon hybridization. Because the specification

does not enable the narrower scope of polynucleotides

claimed in the ’180 patent, it also cannot enable the

broader scope of polynucleotides claimed in the ’405

patent. As such, even though the asserted claims of the

’405 patent pertain to certain processes, the claims are

still not enabled for the reasons described with respect

to the ’180 patent.

In sum, viewing the evidence in the light most

favorable to Enzo, we agree with the district court’s grant

of summary judgment.

For the foregoing reasons, we affirm the district

court’s grant of summary judgment that the asserted

claims of the ’180 patent and the ’405 patent are invalid

for lack of enablement.

AFFIRMED

19a

Appendix B

Appendix b — memorandum

opinion of

the united states district court for

the district of delaware,

filed august 15, 2017

in the United States District Court

for the District of Delaware

C.A. No. 12-274-LPS

ENZO LIFE SCIENCES, INC.,

Plaintiff,

ABBOTT LABORATORIES

and ABBOTT MOLECULAR, INC.,

Defendants.

August 15, 2017, Decided;

August 15, 2017, Filed

MEMORANDUM OPINION

STARK, U.S. District Judge:

Pending before the Court are: (i) Defendants Abbott

Laboratories and Abbott Molecular Inc.’s (collectively,

“Abbott” or “Defendants”) Motion for Summary Judgment

of Invalidity of U.S. Patent No. 8,097,405 (the “’405 patent”)

for Failure to Comply with the Written Description

20a

Appendix B

Requirement (D.I. 413 at 6-16), and (ii) Abbott’s Motion

for Summary Judgment of Invalidity of the ’405 Patent

for Nonenablement (D.I. 458). For the reasons set forth

below, the Court will deny Abbott’s motion with respect

to written description and will grant Abbott’s motion with

respect to nonenablement.

I. BACKGROUND

Plaintiff Enzo Life Sciences, Inc. (“Enzo” or

“Plaintiff”) filed this patent infringement action against

Abbott, alleging infringement of the ’405 patent as well

as U.S. Patent No. 6,992,180 (“the ’180 patent”).

The ’405 patent, which is the subject of the pending

motions, generally pertains to non-radioactive labeling

and “relate[s] to nucleic acid1 detection technology that

relies upon the ability of nucleic acid (DNA or RNA)

strands to hybridize — or bind together.” (D.I. 430 at 7)

(internal quotation marks omitted) While “the prevailing

perception in the art [at the time of the invention] was

that specific base moieties (the so-called ‘Ward’ positions)

were the only possible positions for labeling,” the ’405

patent discloses that nucleotides “with non-radioactive

labels attached to certain positions of a nucleotide — the

phosphate moiety, sugar moiety, or non-Ward positions on

the base moiety — could . . . be used as detectable nucleic

acid probes.” (D.I. 423 at 5-6 (emphasis omitted); see also

D.I. 427 at A2130)

1. “Nucleic acids (DNA or RNA) are made up of ‘nucleotide[s],’

each of which ‘typically consists of three parts: a base, a sugar, and

a phosphate.”’ (D.I. 430 at 7) (quoting D.I. 431-2 Ex. 16 at 9)

21a

Appendix B

The ’405 patent was issued on January 17, 2012 and

claims priority to June 23, 1982. (See D.I. 423 at 6) The

asserted claims of the ’405 patent “fall into two categories:

the in situ hybridization claims and the liquid phase

claims.” (D.I. 430 at 8) The in situ hybridization claims —

claims 63, 64, 65, 94, 103, 128, and 144 — “recite processes

for counting or identifying chromosomes through ‘specific

hybridization’ to a ‘locus or loci’ of a chromosome, using

probes labeled at specified positions.” (Id.) The liquid phase

claims — claims 196 and 198 — “specify permissible Sigs

[detectable labels] and detection methods, respectively.” 2

(Id. at 9)

Abbott moved for summary judgment of invalidity of

the ’405 patent for lack of written description on May 12,

2. Claims 94, 103, 128, and 144 depend from independent claims

63, 64, and 65, among other claims. Claims 196 and 198 depend from

independent claims 188 and 189, both of which recite the following

limitations that are pertinent here:

A process for detecting the presence of a nucleic

acid of interest in a sample, comprising: providing

or generating (i) a detectable non-radioactively

labeled oligonucleotide or polynucleotide, . . . and (ii)

a sample that may contain said nucleic acid of interest;

forming in liquid phase, hybrids comprising said

detectable non-radioactively labeled oligonucleotide

or polynucleotide specifically hybridized with said

nucleic acid of interest; and detecting hybrids nonradioactively to detect the presence of said nucleic

acid of interest.

(’405 patent col. 54 ll. 31-67, col. 55 ll. 1-10)

22a

Appendix B

2017 (D.I. 410 at 6-16; D.I. 413 at 6-16), 3 and the parties

completed briefing on July 7, 2017 (D.I. 413, 423, 448).

On June 28, 2017, while summary judgment briefing was

underway, the Court issued a Memorandum Opinion in

a related case, Enzo Life Sciences, Inc. v. Gen-Probe

Inc., C.A. No. 12-104-LPS, granting a defense motion for

summary judgment that the asserted claims of the ’180

patent are invalid for nonenablement. (C.A. No. 12-104LPS D.I. 284) (“Gen-Probe Opinion” or “GP Op.”) On the

same day, the Court issued an oral order in the instant

case, requiring the parties to submit a joint status report

discussing their respective position(s) on how the Court

should proceed with respect to the summary judgment

motions pending here. (D.I. 441)

In their July 10 status report, the parties agreed that

the Gen-Probe Opinion invalidated all of the ’180 patent

claims asserted against Abbott and that all pending

motions pertaining to the ’180 patent were now moot. (See

D.I. 450 at 4-5) The status report also included Abbott’s

request for leave to file a motion for summary judgment

of invalidity of the ’405 patent for nonenablement. (See id.

at 6) In Abbott’s view, good cause was established by the

Gen-Probe Opinion, because “the ’405 patent is related

to and has essentially the same specification as the ’180

patent.” (Id. at 5)

The Court granted Abbott’s request for leave. (D.I.

451) Thereafter, between July 18 and August 1, 2017, the

3. D.I. 413 is an amendment to Abbott’s opening brief, D.I. 410,

and was filed on May 12, 2017. When citing to Abbott’s opening brief,

this Memorandum Opinion refers to D.I. 413, not D.I. 410.

23a

Appendix B

parties submitted additional letter briefing with respect

to enablement. (D.I. 459, 461, 462) The Court heard oral

argument on August 8, 2017. (See Transcript (“Tr.”))

II. LEGAL STANDARDS

A. Summary Judgment

Under Rule 56(a) of the Federal Rules of Civil

Procedure, “[t]he court shall grant summary judgment if

the movant shows that there is no genuine dispute as to

any material fact and the movant is entitled to judgment

as a matter of law.” The moving party bears the burden of

demonstrating the absence of a genuine issue of material

fact. See Matsushita Elec. Indus. Co., Ltd. v. Zenith

Radio Corp., 475 U.S. 574, 585-86, 106 S. Ct. 1348, 89 L.

Ed. 2d 538 (1986). An assertion that a fact cannot be — or,

alternatively, is — genuinely disputed must be supported

either by “citing to particular parts of materials in the

record, including depositions, documents, electronically

stored information, affidavits or declarations, stipulations

(including those made for purposes of the motion only),

admissions, interrogatory answers, or other materials,”

or by “showing that the materials cited do not establish

the absence or presence of a genuine dispute, or that an

adverse party cannot produce admissible evidence to

support the fact.” Fed. R. Civ. P. 56(c)(1)(A) & (B). If the

moving party has carried its burden, the nonmovant must

then “come forward with specific facts showing that there

is a genuine issue for trial.” Matsushita, 475 U.S. at 587

(internal quotation marks omitted). The Court will “draw

all reasonable inferences in favor of the nonmoving party,

24a

Appendix B

and it may not make credibility determinations or weigh

the evidence.” Reeves v. Sanderson Plumbing Prods., Inc.,

530 U.S. 133, 150, 120 S. Ct. 2097, 147 L. Ed. 2d 105 (2000).

To defeat a motion for summary judgment, the

nonmoving party must “do more than simply show that

there is some metaphysical doubt as to the material facts.”

Matsushita, 475 U.S. at 586; see also Podobnik v. U.S.

Postal Serv., 409 F.3d 584, 594 (3d Cir. 2005) (stating party

opposing summary judgment “must present more than

just bare assertions, conclusory allegations or suspicions

to show the existence of a genuine issue”) (internal

quotation marks omitted). The “mere existence of some

alleged factual dispute between the parties will not defeat

an otherwise properly supported motion for summary

judgment;” a factual dispute is genuine only where “the

evidence is such that a reasonable jury could return a

verdict for the nonmoving party.” Anderson v. Liberty

Lobby, Inc., 477 U.S. 242, 247-48, 106 S. Ct. 2505, 91 L.

Ed. 2d 202 (1986). “If the evidence is merely colorable, or

is not significantly probative, summary judgment may be

granted.” Id. at 249-50 (internal citations omitted); see

also Celotex Corp. v. Catrett, 477 U.S. 317, 322, 106 S. Ct.

2548, 91 L. Ed. 2d 265 (1986) (stating entry of summary

judgment is mandated “against a party who fails to

make a showing sufficient to establish the existence of an

element essential to that party’s case, and on which that

party will bear the burden of proof at trial”). Thus, the

“mere existence of a scintilla of evidence” in support of

the nonmoving party’s position is insufficient to defeat a

motion for summary judgment; there must be “evidence on

which the jury could reasonably find” for the nonmoving

party. Anderson, 477 U.S. at 252.

25a

Appendix B

B. Patent Validity Under 35 U.S.C. § 112

Paragraph 1 of 35 U.S.C. § 112 4 states in pertinent

part:

The specification shall contain a written

description of the invention and of the manner

and process of making and using it, in such full,

clear, concise and exact terms as to enable any

person skilled in the art to which it pertains, or

with which it is most nearly connected, to make

and use the same . . . .

The statute sets out separate requirements for written

description and enablement. See Ariad Pharms., Inc. v. Eli

Lilly & Co., 598 F.3d 1336, 1344 (Fed. Cir. 2010) (holding

that written description and enablement requirements

are separate). Nonetheless, these requirements “often

rise and fall together.” Id. at 1352.

1. Written Description

Whether a specification satisfies the written description

requirement is a question of fact. See GlaxoSmithKline

LLC v. Banner Pharmacaps, Inc., 744 F.3d 725, 729 (Fed.

Cir. 2014); see also Alcon, Inc. v. Teva Pharms. USA, Inc.,

664 F. Supp. 2d 443, 468 (D. Del. 2009) (“Satisfaction of the

4. The patent statute was amended in September 2011 by the

America Invents Act (“AIA”). See Leahy-Smith America Invents

Act, Pub. L. No. 112-29, 125 Stat. 284, 300-01 (2011). The pre-AIA

version of § 112 applies in this case. The post-AIA version of this

portion of the statute (§ 112(a)) is identical to the pre-AIA verison.

26a

Appendix B

written description requirement is a fact-based inquiry,

depending on ‘the nature of the claimed invention and the

knowledge of one skilled in the art at the time an invention

is made and a patent application is filed.’”) (quoting

Carnegie Mellon Univ. v. Hoffinann-La Roche Inc., 541

F.3d 1115, 1122 (Fed. Cir. 2008)). Despite being a question

of fact, the issue of invalidity for lack of written description

can be amenable to summary judgment. See, e.g., Carnegie

Mellon, 541 F.3d at 1126-28 (affirming summary judgment

of invalidity for lack of written description); see also

Helicos Biosciences Corp. v. Illumina, Inc., 888 F. Supp.

2d 519, 530-31 (D. Del. 2012) (“While compliance with the

written description requirement is a question of fact, the

issue is ‘amenable to summary judgment in cases where no

reasonable fact finder could return a verdict for the nonmoving party.’”) (quoting Power Oasis, Inc. v. T-Mobile

USA, Inc., 522 F.3d 1299, 1307 (Fed. Cir. 2008)).

To comply with the written description requirement,

a patent’s specification “must clearly allow persons of

ordinary skill in the art to recognize that the inventor

invented what is claimed.” Ariad, 598 F.3d at 1351

(internal brackets and quotation marks omitted).

“[T]he test for sufficiency is whether the disclosure of the

application relied upon reasonably conveys to those skilled

in the art that the inventor had possession of the claimed

subject matter as of the filing date.” Id. “[T]he hallmark

of written description is disclosure. Thus, ‘possession as

shown in the disclosure’ is a more complete formulation”

of the written description requirement. Id. “[T]he test

requires an objective inquiry into the four comers of

the specification from the perspective of a person of

27a

Appendix B

ordinary skill in the art.” Id. “[T]he written description

requirement does not demand either examples or an actual

reduction to practice; a constructive reduction to practice

that in a definite way identifies the claimed invention can

satisfy the written description requirement.” Id. at 1352.

However, “a description that merely renders the invention

obvious does not satisfy the requirement.” Id.

2. Enablement

“Enablement is a question of law based on underlying

factual findings.” MagSil Corp. v. Hitachi Glob. Storage

Techs., Inc., 687 F.3d 1377, 1380 (Fed. Cir. 2012). “To be

enabling, the specification of a patent must teach those

skilled in the art how to make and use the full scope of

the claimed invention without undue experimentation.”

Id. (internal quotation marks omitted). “Enablement

serves the dual function in the patent system of ensuring

adequate disclosure of the claimed invention and of

preventing claims broader than the disclosed invention.”

Id. at 1380-81. “Thus, a patentee chooses broad claim

language at the peril of losing any claim that cannot be

enabled across its full scope of coverage.” Id. at 1381. “The

scope of the claims must be less than or equal to the scope

of the enablement to ensure that the public knowledge is

enriched by the patent specification to a degree at least

commensurate with the scope of the claims.” Id. (internal

quotation marks omitted).

“ Whether undue experimentation is needed is

not a single, simple factual determination, but rather

is a conclusion reached by weighing many factual

28a

Appendix B

considerations.” In re Wands, 858 F.2d 731, 737 (Fed.

Cir. 1988). These factors include “(1) the quantity of

experimentation necessary, (2) the amount of direction or

guidance presented, (3) the presence or absence of working

examples, (4) the nature of the invention, (5) the state of

the prior art, (6) the relative skill of those in the art, (7)

the predictability or unpredictability of the art, and (8)

the breadth of the claims.” Id. Although “a specification

need not disclose what is well known in the art,” “[t]ossing

out the mere germ of an idea does not constitute enabling

disclosure.” Genentech, Inc. v. Novo Nordisk A/S, 108

F.3d 1361, 1366 (Fed. Cir. 1997). A patent “cannot simply

rely on the knowledge of a person of ordinary skill to

serve as a substitute for the missing information in the

specification.” ALZA Corp. v. Andrx Pharms., LLC, 603

F.3d 935, 941 (Fed. Cir. 2010).

III. DISCUSSION

A. Written Description

1. Written Description for Hybridization and

Detection of Probes Labeled at Non-Ward

Positions

Abbott seeks summary judgment that the ’405 patent

contains insufficient written description for non-Wardlabeled probes used for hybridization and detection.

(See D.I. 413 at 9) In Abbott’s view, the ’405 patent

specification “at best describes that probes . . . labeled

at non-Ward positions could be made, would hybridize

to complementary nucleic acids of interest, and would be

29a

Appendix B

detected,” but describes no such testing. (Id. at 11) Abbott

further contends that “it would have been necessary to

make and test [a non-Ward-labeled probe]” because, as of

the priority date, “non-Ward labeling was believed to be

disruptive and unsuitable” and the Ward patent 5 taught

away from attaching a non-radioactive label to any position

other than a Ward position. (Id. at 9, 11 (internal quotation

marks omitted; alteration in original); see also D.I. 411-4

Ex. 21 at 63)

Enzo responds that the specification “provide[s]

numerous specific examples of labeling probes at . . . nonWard positions.” (D.I. 423 at 14) Specifically, Enzo contends

that Example V discloses phosphate labeling (see ’405

patent col. 5 11. 40-53); Example XXXIII describes base

labeling at non-Ward positions (see ’405 patent col. 4 11.

16-24, col. 13 11. 23-53); and the specification describes

labeling at the sugar moiety (see ’405 patent col. 3 11. 4553). (See D.I. 423 at 14-15) Enzo further contends that the

specification discloses that “hybridization and detection

are the plain purposes to which each of the above examples

are directed.” (Id. at 15; see also ’405 patent col. 29 11.

34-38) According to Enzo, a person of ordinary skill in

the art (“POSA”) would have “understood each of the

examples discussed above to be a complete embodiment

of the claimed probes” (D.I. 423 at 15 n.10) (emphasis

omitted) and would have also been aware of “a variety of

additional chemistries” for labeling at non-Ward positions

5. The Ward patent discloses labeling at the Ward positions

of the base moiety. The ’405 patent incorporates by reference the

specification of the Ward patent. (See D.I. 413 at 7; ’405 patent col.

3 ll. 15-17)

30a

Appendix B

(id. at 16). Thus, in Enzo’s view, “[a]t a minimum, the

presence of numerous specific examples of the inventions,

and both sides’ expert opinions regarding those examples,

creates disputes of material fact,” precluding summary

judgment. (Id. at 17)

The Court agrees with Enzo that genuine disputes of

material fact preclude summary judgment on whether the

’405 patent contains sufficient written description for nonWard-labeled probes used for hybridization and detection.

(See, e.g., D.I. 411-4 Ex. 21 at 63; D.I. 427 at A2331-55; ’405

patent col. 29 11. 34-38) A reasonable factfinder could find,

as Abbott contends, that no portion of the specification

discloses non-Ward-labeled probes that could successfully

hybridize or be detected. (See D.I. 413 at 9, 11) By contrast,

a reasonable factfinder could also find, as Enzo asserts,

that various parts of the specification disclose non-Wardlabeled polynucleotides that are useful for hybridization

and detection. (See D.I. 423 at 14-16)

Accordingly, the Court will deny this portion of

Abbott’s motion for summary judgment.

2. Written Description for the In Situ

Hybridization Claims

Abbott seeks summary judgment that the ’405 patent

lacks adequate written description for the claimed

processes recited in the in situ hybridization claims —

specifically, the processes for “determining whether the

number of copies of a particular chromosome in a cell

is normal or abnormal,” “identifying a chromosome of

31a

Appendix B

interest in a cell containing other chromosomes,” and

“identifying a plurality or all of the chromosomes of a

cell of interest.” (D.I. 413 at 15; see also ’405 patent col.

34 ll. 62-64, col. 36 ll. 1-2, col. 37 ll. 7-8) Abbott contends

that “[t]he only portions of the ’405 patent [that] Enzo

identifies as containing any disclosure of th[ose] processes

are the title and abstract,” both of which were added 20

years after the priority date. (D.I. 413 at 15-16) (emphasis

omitted) Abbott further contends that Example 9 of the

Ward patent cannot provide adequate written description

for the in situ hybridization claims because that Example

was prophetic and could not be practiced until 1996. (See

id. at 16; D.I. 411-4 Ex. 27 at 31-34)

Enzo counters that Example 9 provides sufficient

written description for the in situ hybridization claims

because Abbott’s own expert admitted that “[c]ertain

embodiments [of Example 9] certainly could be practiced

without question” in 1981. (D.I. 425 at A809; see also

D.I. 423 at 19 n.10) Enzo further contends that “in situ

hybridization with human and nonhuman chromosomes

was well known by 1982” and, therefore, was available to

a POSA as of the priority date. (D.I. 423 at 9)

The Court concludes that the record reveals a genuine

dispute of material fact with respect to whether Example

9 could be practiced before the priority date. While Abbott

contends that the relevant portions of Example 9 could

not be practiced until approximately 14 years after the

priority date (see D.I. 411-4 Ex. 27 at 31-34), Enzo cites

record evidence that “[c]ertain embodiments . . . certainly

could be practiced without question” before the priority

32a

Appendix B

date (D.I. 425 at A809). A reasonable jury, viewing such

evidence, could find for either Abbott or Enzo on this

dispute.

Accordingly, the Court will deny this portion of

Abbott’s motion for summary judgment.

3. Written Description for the Liquid Phase

Claims

Abbott requests that the Court grant summary

judgment that the ’405 patent lacks adequate written

description for the liquid phase claims. In support, Abbott

argues that the specification of the ’405 patent “does not

describe any oligo-or polynucleotide . . . used for specific

hybridization in liquid phase to detect a nucleic acid of

interest in a sample,” as required by the liquid phase

claims. (D.I. 413 at 13)

Enzo responds that the specification “explicitly

descr ibe[s]” the probes useful for “detection or

hybridization in the liquid phase between the DNA sought

to be detected and the DNA detecting probe.” (D.I. 423 at

15 (internal quotation marks omitted); see also ’405 patent

col. 19 11. 63-65; col. 20 11. 1-10)) Enzo further asserts

that “[h]ybridization in the liquid phase was known in the

art” and, therefore, available to a POSA as of the priority

date. (D.I. 423 at 9)

The record demonstrates genuine disputes of

fact with respect to whether the ’405 patent contains

adequate written description for the liquid phase claims.

33a

Appendix B

A reasonable jury could find for either side, based on the

record evidence. (See, e.g., D.I. 411-4 Ex. 28 at 163; ’405

patent col. 19 ll. 63-65, col. 20 ll. 1-10)

Accordingly, the Court will deny this portion of

Abbott’s motion for summary judgment.

B. Enablement

Abbott seeks summary judgment that the asserted

claims of the ’405 patent are invalid for nonenablement

on the basis of the Court’s reasoning in the Gen-Probe

Opinion. (See GP Op.) (granting summary judgment

that asserted claims of ’180 patent are invalid for

nonenablement) In Abbott’s view, the Court’s reasoning

in the Gen-Probe Opinion supports invalidating the ’405

patent on enablement grounds because “[a] specification6

that does not enable the narrower scope of polynucleotides

claimed in the ’180 patent cannot enable the broader scope

of polynucleotides recited in the ’405 patent.” (D.I. 459 at

1; see also Tr. at 6-7, 17) Abbott further contends that the

claims of the ’405 patent, like those of the ’180 patent, “do

not limit the length or sequence of the polynucleotides

and, thus, cover [the] use of at least the same millions

(or more) phosphate-labeled polynucleotides that were

not enabled in the ’180 patent.” (D.I. 459 at 1) (internal

quotation marks omitted)

With respect to other polynucleotides labeled at nonWard positions, Abbott asserts that Enzo “cannot identify

6. It is undisputed that the specifications of the ’405 patent and

’180 patent are identical in relevant part. (See Tr. at 6)

34a

Appendix B

any Example [in the ’405 patent’s specification] that

describes [the] chemistry for the vast majority of the other

non-Ward labeling positions that the ’405 patent seeks to

capture,” including the chemistry for all non-Ward base

labeling positions. (Id. at 2) Abbott further argues that the

methods disclosed in the asserted claims are not enabled

because Enzo’s expert, Dr. Sherman, admitted that “there

[is] no data in the ’405 patent showing that a probe labeled

at a non-Ward position . . . would successfully hybridize.”

(D.I. 459-1 Ex. 6 at 193-94) According to Abbott, the lack

of any such experiment being reported in the specification

establishes that a POSA would have had to engage in

“undue experimentation” in order to confirm that nonWard-labeled probes work, given the “vast number of

possible variants to the claimed invention.” (D.I. 459 at

2) (internal quotation marks omitted)

Enzo responds that “the ’405 [p]atent specification

descr ibes in g reat detail a w ide var iety of nonradioactively[-]labeled polynucleotides that can be used

in the claimed methods, including probes labeled . . . at

. . . non-Ward positions.” (D.I. 461 at 3) (citing ’405 patent

col. 3 ll. 20-67, col. 4 ll. 1-24, col. 5 ll. 40-53, col. 12 ll. 4867, col. 13 ll. 1-54, col. 22 ll. 56-67, cols. 23-24, col. 25 ll.

1-66 as disclosing probes labeled at sugar, phosphate,

and certain base moieties) Enzo further contends that

“skilled artisans were aware of additional chemistries for

attaching labels at the other non-Ward positions” that are

not explicitly disclosed in the specification. (Id.) In Enzo’s

view, the variations in “polynucleotide sequence, length,

labels, linkers, and position of labeling” would not “render

any application of the claimed methods inoperable” and,

35a

Appendix B

therefore, a POSA could practice the invention “without

engaging in undue (if any) experimentation.” (Id. at 2-3)

(emphasis omitted)

According to Enzo, the specific limitations recited

in the asserted claims are adequately described in the

specification or were already known in the art. With

respect to the in situ hybridization claims in particular,

Enzo notes that Abbott’s expert admitted that “the

practice of the claimed methods would have been enabled

with over 50 different probe designs and that deploying

those alleged probes in the claimed in situ hybridization

processes would have yielded predictable results.” (D.I.

461 at 5) (internal quotation marks and emphasis omitted)

Enzo further contends that the specification’s disclosure

of probes labeled at non-Ward positions would also have

enabled a POSA to practice the in situ hybridization

claims. (See id. at 4; see also id. at 3)

At oral argument, Enzo’s counsel further argued

that the embodiments recited in the liquid phase claims

were “irrelevant” because “[t]he novelty of liquid phase

hybridization claims lies . . . in the inventive combination

of performing liquid phase hybridization with a nonradioactive probe, whatever the structure of the probe,

followed by detection.” (Tr. at 24-25) As such, in Enzo’s

view, “the exact nature, structure, location of labeling,

sequence, etc. of the non-radioactive[ly]-labeled probe is

tangential to the invention” and, thus, cannot “render the

invention [recited in the liquid phase claims] invalid for

lack of enablement.” (See id. at 26-27; see also id. at 31-32

(citing ’405 patent col. 19 11. 62-67, col. 20 11. 2-10, 26-43 as

36a

Appendix B

providing support for counsel’s argument that “the novelty

[of the invention] . . . lies in the use of [a] particular type of

hybridization in the liquid phase . . . using non-radioactive

labels, followed by detection of those labels”))

In its reply, Abbott argues that Enzo’s opposition

“repeat[s] arguments that the Court has already rejected”

in the Gen-Probe Opinion. (D.I. 462 at 1) (emphasis

omitted) Specifically, Abbott notes that even though

the Court has already concluded that “no ‘part[] of the

specification indicates whether an internal phosphatelabeled polynucleotide maintain[s] hybridizability

and detectability’” (id.) (quoting GP Op. at 15; second

alteration in original), Enzo insists that the specification

of the ’405 patent “‘completely’ discloses polynucleotides

‘labeled at the phosphate moiety’” (id.) (quoting D.I. 461

at 1). In Abbott’s view, given the lack of disclosure in

the specification, a POSA would be required to engage

in undue experimentation to identify and determine

whether the claimed phosphate-, sugar-, and baselabeled polynucleotides “might be useful in the claimed

processes.” (Id.) Abbott further contends that a POSA

would have considered non-Ward-labeled probes to be

inoperative, in view of the state of the art at the pertinent

time. (See id. at 2)7

While Enzo contends that the specification discloses

the limitations of the asserted claims, Abbott replies that

7. The Court agrees with Abbott that while inoperability can

be a basis for nonenablement, it is not a prerequisite to a finding of

nonenablement. (See D.I. 462 at 2) (citing Wyeth & Cordis Corp. v.

Abbott Labs., 720 F.3d 1380, 1384 (Fed. Cir. 2013))

37a

Appendix B

“[t]he ’405 patent does not describe the claimed in situ

hybridization processes at all” and also fails to “describe[]

. . . the conditions (e.g. probe concentration, temperature,

salt concentration, etc.) under which the [liquid-phase]

process[es] can occur.” (Id.) (citing testimony of Enzo’s

expert that liquid-phase hybridization “depends on such

conditions”) Abbott further asserts that the distinction

between the ’180 and ’405 patent claims “makes no

difference” to the Court’s analysis: although “the ’180

patent claims products [and] the ’405 patent claims

processes,” the claimed processes of the ’405 patent

“depend on the hybridizability and detectability of the

claimed probes.” (Id.) “Without enabled probes,” Abbott

argues, “the processes [claimed in the ’405 patent] cannot

be enabled.” (Id.; see also id. at 1 (arguing that certain

probes are not enabled to maintain hybridizability and

detectability); Tr. at 9 (counsel for Abbott asserting that

“[t]he ’405 patent claims are process claims, but this only

makes them less enabled, not more”))

“To prove that a claim is invalid for lack of enablement,

a challenger must show by clear and convincing evidence

that a person of ordinary skill in the art would not be

able to practice the claimed invention without ‘undue

experimentation.’” Alcon Research Ltd. v. Barr Labs.,

Inc., 745 F.3d 1180, 1188 (Fed. Cir. 2014) (quoting Wands,

858 F.2d at 736-37). Having applied this standard to the

record evidence, and taking that evidence in the light most

favorable to Enzo as the non-moving party, the Court

concludes that there is no genuine dispute of fact that

the asserted claims of the ’405 patent are nonenabled. A

reasonable jury could not find for Enzo. Instead, the only

38a

Appendix B

conclusion a reasonable jury could reach is that clear and

convincing evidence proves the ’405 patent is invalid for

noneablement.

“[T]he specification must teach those of skill in the art

how to make and how to use the invention as broadly as

it is claimed.” In re Goodman, 11 F.3d 1046, 1050 (Fed.

Cir. 1993) (internal quotation marks omitted; emphasis

added). Here, even though the specifications of the ’180

and ’405 patents are identical in all relevant respects,

the asserted claims of the ’405 patent are even broader

than the asserted claims of the ’180 patent that the Court

invalidated as nonenabled in the Gen-Probe Opinion. (See

GP Op.; D.I. 449-1 Ex. 4 at 148-49) Given the breadth of

the asserted claims and given the Court’s conclusions in

the Gen-Probe Opinion, the Court agrees with Abbott

that “[a] specification that does not enable the narrower

scope of polynucleotides claimed in the ’180 patent cannot

enable the broader scope of polynucleotides recited in the

’405 patent.” (D.I. 459 at 1)

Enzo argues that the specification of the ’405 patent

adequately describes “the broader scope of [non-Wardlabeled] polynucleotides recited in the ’405 patent.” (Id.;

see also D.I. 461 at 3 (citing parts of specification that

describe claimed polynucleotides)) But the Court already

rejected this contention in the Gen-Probe Opinion, finding

that no “part[] of the specification indicates whether an

internal phosphate-labeled polynucleotide maintain[s]

hybridizability and detectability.” (GP Op. at 15 (internal

quotation marks omitted; second alteration in original);

see also Amgen, Inc. v. Genetics Inst., Inc., 98 F.3d 1328,

39a

Appendix B

1331 (Fed. Cir. 1996) (“[S]ince the ‘195 specification did

not enable EPO having a specific activity of at least

160,000 IU/AU, enablement of that product could not be

relitigated for the identical ‘837 specification.”)) Similarly,

with respect to the ’405 patent in particular, no part of

the specification discloses base labeling at all non-Ward

positions, much less whether all non-Ward base-labeled

probes would maintain hybridizability and detectability.

(See D.I. 459 at 2; see also Genentech, 108 F.3d at 1366

(“Patent protection is granted in return for an enabling

disclosure of an invention, not for vague intimations of

general ideas that may or may not be workable.”)). Given

the claims’ scope and the specification’s limited disclosure,

Abbott correctly asserts that a POSA “would have no

choice but to make and test a vast number of possible

variants to the claimed invention.” (D.I. 459 at 2) (internal

quotation marks omitted) Undue experimentation would

be required, rendering the claims non-enabled.

That the asserted claims are process claims does

nothing to reduce the amount of experimentation required.

This is because each process in the asserted claims

“depend[s] on the hybridizability and detectability of the

claimed probes.” (D.I. 462 at 2) But since the specification

does not enable the claimed probes — no “part[] of the

specification indicates whether an internal phosphatelabeled polynucleotide maintain[s] hybridizability and

detectability,” and no part of the specification discloses

base labeling at all non-Ward positions (GP Op. at 15

(internal quotation marks omitted; second alteration in

original); see also Tr. at 9 (counsel for Abbott stating

that “[i]f the polynucleotide is not enabled at all, . . . the

40a

Appendix B

processes using that polynucleotide cannot be enabled”))

— the processes recited in the asserted claims of the ’405

patent are also non-enabled.

The Court agrees with Abbott’s comparison of the

present situation to that confronted by the Federal Circuit

in Wyeth & Cordis Corp. v. Abbott Labs., 720 F.3d 1380

(Fed. Cir. 2013). In Wyeth, the Federal Circuit affirmed

a grant of summary judgment based on nonenablement.

See id. at 1386. Here, “(1) the claims are far broader than

in Wyeth, 8 (2) the disclosures here are far less than in

Wyeth,9 (3) the relevant field is even more unpredictable

than in Wyeth,10 and (4) the trial-and-error process would

have taken even longer than in Wyeth.”11 (GP Op. at 15)

8. As Abbott argues, “the millions (or more) of [non-Ward]labeled polynucleotides with varying sequences and lengths covered

by each asserted claim of the [’405] patent far exceed the tens of

thousands of sirolimus analogs in Wyeth and the millions or more of

phosphate-labeled polynucleotides covered by the ’180 patent.” (D.I.

459 at 3) (internal quotation marks omitted; alterations in original)

9. Abbott argues that, “[w]hile the specification in Wyeth

disclosed at least one working example of the claimed invention

(sirolimus) . . . , the [’405] patent discloses none.” (D.I. 459 at 3)

(internal quotation marks omitted; second alteration in original)

Abbott further points out that, “unlike for the ’180 patent, Enzo

does not even argue that there is a prophetic example showing the

labeling chemistry for each non-Ward position.” (Id.)

10. Abbott notes that “Enzo’s own expert explicitly admitted

that, in 1982, there was ‘no’ ‘ab[ility] to predict which chemical

transformations and which label types and positions would be likely

to work.’” (D.I. 459 at 3) (quoting D.I. 459-1 Ex. 6 at 148)

11. Abbott contends, “[t]he [trial-and-error] process would have

been even longer for the ’405 patent than for the ’180 patent because

the claimed scope of polynucleotides is greater.” (D.I. 459 at 3)

41a

Appendix B

(internal quotation marks omitted) It follows that here,

as in Wyeth, there is no genuine dispute that the claims

are invalid due to nonenablement.

This same conclusion is supported by consideration

of the Wands factors. See 858 F.2d at 737. Based on

the record, a reasonable factfinder could only find: “(1)

the quantity of experimentation necessary to arrive at

embodiments equal to the full scope of the claims is undue;

(2) insufficient direction or guidance is presented in the

patent to allow a POSA to avoid undue experimentation;

(3) insufficient working examples are present; 12 (4)

the invention arises in a field of art that was highly

unpredictable at the time of the invention; (5) the prior

art showed that the pertinent field was unpredictable; (6)

even though the relative skill of those in the art was high,

POSAs at the time did not have sufficient knowledge to

fill in all that is missing from the patent; (7) the art was,

as already noted, highly unpredictable; and (8) the claims

are extremely broad.” (GP Op. at 16) (internal quotation

marks omitted)

Enzo opposes this conclusion, arguing that the liquid

phase claims are enabled because “the exact nature,

structure, location of labeling, sequence, etc. of the nonradioactive[ly] PA-labeled probe is tangential” to the

invention recited in the liquid phase claims. (Tr. at 27) As

stated above, however, the processes claimed in the liquid

phase claims cannot be enabled if the polynucleotides

12. Abbott notes that the specification contains no working

examples for any non-Ward position. (See D.I. 459 at 3)

42a

Appendix B

are not enabled. (See id. at 9) Moreover, even if one such

process with one particular embodiment were enabled,

that would still fail to enable the full scope of the liquid

phase claims. This is because a POSA at the pertinent

time had “no” “ab[ility] to predict which chemical

transformations and which label types and positions would

be likely to work,” according even to Enzo’s expert, Dr.

Sherman. (D.I. 459-1 Ex. 6 at 148) Thus, the presence of

one enabling embodiment would be insufficient to enable

the entire scope of the claim, as of the priority date. See

In re Goodman, 11 F.3d at 1050 (“[T]he specification must

teach those of skill in the art how to make and how to use

the invention as broadly as it is claimed.”).

Accordingly, the Court will grant Abbott’s motion

for summary judgment that the ’405 patent is invalid for

nonenablement.13

13. The Court is not persuaded by Enzo’s citation to Delaware

Display Group LLC v. Vizio, Inc., 2017 U.S. Dist. LEXIS 28656, 2017

WL 784988, at *5 (D. Del. Mar. 1, 2017), in which Judge Andrews

rejected a nonenablement challenge, reasoning that tangential, nonnovel aspects of claims do not require enablement. Here, the record

would not permit a reasonable factfinder to find that all of what is

nonenabled in the liquid phase claims of the ’405 patent is non-novel

or tangential to the claimed invention. (See D.I. 427 at A2130 (“There

was skepticism in the art about non-radioactively labeling a nucleic

acid probe at a position other than the Ward positions before June

23, 1982.”); id. at A2134 (stating that invention claimed in ’405 patent

“facilitates the use of non-radioactive labels in the hybridization

[and] detection process”))

43a

Appendix B

IV. CONCLUSION

For the foregoing reasons, the Court will deny

Abbott’s motion with respect to the written description

requirement and will grant Abbott’s motion with respect

to nonenablement. An appropriate Order follows.

44a

Appendix C

Appendix c — memorandum

opinion of

the united states district court for

the district of delaware,

filed june 28, 2017

IN THE United States District Court

for the District of Delaware

June 28, 2017, Decided;

June 28, 2017, Filed

C.A. No. 12-104-LPS

ENZO LIFE SCIENCES, INC.,

Plaintiff,

GEN-PROBE INCORPORATED,

Defendant.

C.A. No. 12-106-LPS

ENZO LIFE SCIENCES, INC.,

Plaintiff,

ROCHE MOLECULAR SYSTEMS, INC.;

ROCHE DIAGNOSTICS CORPORATION; ROCHE

DIAGNOSTICS OPERATIONS, INC.; and ROCHE

NIMBLEGEN, INC.,

Defendants.

45a

Appendix C

C.A. No. 12-275-LPS

ENZO LIFE SCIENCES, INC.,

Plaintiff,

BECTON, DICKINSON AND COMPANY;

BECTON DICKINSON DIAGNOSTICS INC.;

and GENOHM SCIENCES, INC.,

Defendants.

C.A. No. 12-276-LPS

ENZO LIFE SCIENCES, INC.,

Plaintiff,

HOLOGIC, INC.,

Defendant.

MEMORANDUM OPINION

June 28, 2017

Wilmington, Delaware

/s/ Leonard P. Stark

46a

Appendix C

STARK, U.S. District Judge:

Pending before the Court are: (i) Defendants Gen-Probe

Inc. (“Gen-Probe”); Roche Molecular Systems, Inc, Roche

Diagnostics Corporation, Roche Diagnostics Operations, Inc.,

and Roche Nimblegen, Inc. (collectively, “Roche”); Becton,

Dickinson and Company, Becton Dickinson Diagnostics

Inc., and Geneohm Sciences, Inc. (collectively, “BD”); and

Hologic, Inc.’s (“Hologic,” and collectively, with Gen-Probe,

Roche, and BD, “Defendants”) Motion for Summary

Judgment of Invalidity of U.S. Patent No. 6,992,180 (the ’180

patent”) for Failure to Comply with the Written Description

Requirement (C.A. No. 12-104-LPS D.I. 227),1 and (ii) GenProbe’s and Hologic’s Motion for Summary Judgment of

Invalidity of the ’180 Patent for Nonenablement (D.I. 221).

For the reasons set forth below, the Court will deny

Defendants’ motion with respect to the written description

requirement and will grant Gen-Probe’s and Hologic’s

motion with respect to nonenablement.

BACKGROUND

Plaintiff Enzo Life Sciences, Inc. (“Plaintiff” or “Enzo”)

filed patent infringement actions against Defendants,

alleging infringement of the ’180 patent as well as U.S.

Patent No. 7,064,197 (“the ‘197 patent”). “The ’180 patent

generally relates to non-radioactive nucleic acid detection

technology,” while “[t]he ‘197 patent generally relates to

nucleic acid hybridization technology involving non-porous

solid supports.” (C.A. No. 12-106-LPS D.I. 260 at 3)

1. Unless otherwise noted, all citations to the docket are to

C.A. No. 12-104-LPS.

47a

Appendix C

The ’180 patent, which is the subject of the pending

motions, was issued on January 31, 2006 and claims

priority to June 23, 1982. (D.I. 247 at 3) Defendants’

motions focus on representative claim 1 of the ’180 patent,

which states, in relevant part:

A n ol igo - or p oly nucleot ide wh ich i s

complementary to a nucleic acid of interest or

a portion thereof, said oligo - or polynucleotide

comprising at least one modified nucleotide or

modified nucleotide analog having the formula

Sig-PM-SM-BASE

wherein . . . said Sig comprises a non-polypeptide,

non-nucleotidyl, non-radioactive label moiety

which can be directly or indirectly detected when

attached to PM or when said modified nucleotide

is incorporated into said oligo-or polynucleotide

or when said oligo - or polynucleotide is

hybridized to said complementary nucleic acid

of interest or a portion thereof, and wherein Sig

comprises biotin, iminobiotin, an electron dense

component, a magnetic component, a metalcontaining component, a fluorescent component,

a chemiluminescent component, a chromogenic

component, a hapten or a combination of any of

the foregoing.

’180 patent col. 5911. 62-67, col. 6011. 1-21. 2

2. All asserted claims include, or depend from claims that

include, the pertinent limitations in representative claim 1. (See

D.I. 228 at 7 n.6)

48a

Appendix C

On December 15, 2016, Defendants moved for

summary judgment of invalidity of the ’180 patent for lack

of written description (D.I. 227) and enablement (D.I. 221).

Enzo filed its briefs in opposition to Defendants’ motions

on February 16, 2017 (D.I. 251 (written description), D.I.

247 (enablement)), and Defendants filed their reply briefs

on March 20, 2017 (D.I. 269 (written description), D.I. 266

(enablement)). The Court heard oral argument on both

motions on April 4, 2017. (See Transcript (“Tr.”))3

II. LEGAL STANDARDS

A. Summary Judgment

Under Rule 56(a) of the Federal Rules of Civil

Procedure, “[t]he court shall grant summary judgment if

the movant shows that there is no genuine dispute as to

any material fact and the movant is entitled to judgment

as a matter of law.” The moving party bears the burden of

demonstrating the absence of a genuine issue of material

fact. See Matsushita Elec. Indus. Co., Ltd. v. Zenith

Radio Corp., 475 U.S. 574, 585-86, 106 S. Ct. 1348, 89 L.

Ed. 2d 538 (1986). An assertion that a fact cannot be — or,

alternatively, is — genuinely disputed must be supported

either by “citing to particular parts of materials in the

record, including depositions, documents, electronically

stored information, affidavits or declarations, stipulations

(including those made for purposes of the motion only),

admissions, interrogatory answers, or other materials,”

3. The Court heard argument at the same time on the parties’

other motions, which will be resolved by separate opinion(s).

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or by “showing that the materials cited do not establish

the absence or presence of a genuine dispute, or that an

adverse party cannot produce admissible evidence to

support the fact.” Fed. R. Civ. P. 56(c)(1)(A) & (B). If the

moving party has carried its burden, the nonmovant must

then “come forward with specific facts showing that there

is a genuine issue for trial.” Matsushita, 475 U.S. at 587

(internal quotation marks omitted). The Court will “draw

all reasonable inferences in favor of the nonmoving party,

and it may not make credibility determinations or weigh

the evidence.” Reeves v. Sanderson Plumbing Prods., Inc.,

530 U.S. 133, 150, 120 S. Ct. 2097, 147 L. Ed. 2d 105 (2000).

To defeat a motion for summary judgment, the

nonmoving party must “do more than simply show that

there is some metaphysical doubt as to the material facts.”

Matsushita, 475 U.S. at 586; see also Podobnik v. U.S.

Postal Serv., 409 F.3d 584, 594 (3d Cir. 2005) (stating party

opposing summary judgment “must present more than

just bare assertions, conclusory allegations or suspicions

to show the existence of a genuine issue”) (internal

quotation marks omitted). The “mere existence of some

alleged factual dispute between the parties will not defeat

an otherwise properly supported motion for summary

judgment;” a factual dispute is genuine only where “the

evidence is such that a reasonable jury could return a

verdict for the nonmoving party.” Anderson v. Liberty

Lobby, Inc., 477 U.S. 242, 247-48, 106 S. Ct. 2505, 91 L.

Ed. 2d 202 (1986). “If the evidence is merely colorable, or

is not significantly probative, summary judgment may be

granted.” Id. at 249-50 (internal citations omitted); see

also Celotex Corp. v. Catrett, 477 U.S. 317, 322, 106 S. Ct.

50a

Appendix C

2548, 91 L. Ed. 2d 265 (1986) (stating entry of summary

judgment is mandated “against a party who fails to

make a showing sufficient to establish the existence of an

element essential to that party’s case, and on which that

party will bear the burden of proof at trial”). Thus, the

“mere existence of a scintilla of evidence” in support of

the nonmoving party’s position is insufficient to defeat a

motion for summary judgment; there must be “evidence on

which the jury could reasonably find” for the nonmoving

party. Anderson, 477 U.S. at 252.

B. Patent Validity Under 35 U.S.C. § 112

Paragraph 1 of 35 U.S.C. § 112 4 states in pertinent

part:

The specification shall contain a written

description of the invention and of the manner

and process of making and using it, in such full,

clear, concise and exact terms as to enable any

person skilled in the art to which it pertains, or

with which it is most nearly connected, to make

and use the same . . . .

The statute sets out separate requirements for written

description and enablement. See Ariad Pharms., Inc. v. Eli

Lilly & Co., 598 F.3d 1336, 1344 (Fed. Cir. 2010) (holding

4. The patent statute was amended in September 2011 by the

America Invents Act (“AIA”). See Leahy-Smith America Invents

Act, Pub. L. No. 112-29, 125 Stat. 284, 300-01 (2011). The pre-AIA

version of § 112 applies in this case. The post-AIA version of this

portion of the statute (§ 112(a)) is identical to the pre-AIA verison.

51a

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that written description and enablement requirements

are separate). Nonetheless, these requirements “often

rise and fall together.” Id. at 1352.

1. Written Description

Whether a specification satisfies the written description

requirement is a question of fact. See GlaxoSmithKline

LLC v. Banner Pharmacaps, Inc., 744 F.3d 725, 729 (Fed.

Cir. 2014); see also Alcon, Inc. v. Teva Pharms. USA, Inc.,

664 F. Supp. 2d 443, 468 (D. Del. 2009) (“Satisfaction of the

written description requirement is a fact-based inquiry,

depending on ‘the nature of the claimed invention and the

knowledge of one skilled in the art at the time an invention

is made and a patent application is filed.”) (quoting

Carnegie Mellon Univ. v. Hoffmann-La Roche Inc., 541

F.3d 1115, 1122 (Fed. Cir. 2008)). Despite being a question

of fact, the issue of invalidity for lack of written description

can be amenable to summary judgment. See, e.g., Carnegie

Mellon, 541 F.3d at 1126-28 (affirming summary judgment

of invalidity for lack of written description); see also

Helicos Biosciences Corp. v. Illumina, Inc., 888 F. Supp.

2d 519, 530-31 (D. Del. 2012) (“While compliance with the

written description requirement is a question of fact, the

issue is ‘amenable to summary judgment in cases where

no reasonable fact finder could return a verdict for the

non-moving party.”) (quoting PowerOasis, Inc. v. T-Mobile

USA, Inc., 522 F.3d 1299, 1307 (Fed. Cir. 2008)).

To comply with the written description requirement,

a patent’s specification “must clearly allow persons of

ordinary skill in the art to recognize that the inventor

52a

Appendix C

invented what is claimed.” Ariad, 598 F.3d at 1351

(internal brackets and quotation marks omitted).

“[T]he test for sufficiency is whether the disclosure of the

application relied upon reasonably conveys to those skilled

in the art that the inventor had possession of the claimed

subject matter as of the filing date.” Id. “[T]he hallmark

of written description is disclosure. Thus, ‘possession as

shown in the disclosure’ is a more complete formulation”

of the written description requirement. Id. “[T]he test

requires an objective inquiry into the four corners of

the specification from the perspective of a person of

ordinary skill in the art.” Id. “[T]he written description

requirement does not demand either examples or an actual

reduction to practice; a constructive reduction to practice

that in a definite way identifies the claimed invention can

satisfy the written description requirement.” Id. at 1352.

However, “a description that merely renders the invention

obvious does not satisfy the requirement.” Id.

2. Enablement

“Enablement is a question of law based on underlying

factual findings.” MagSil Corp. v. Hitachi Glob. Storage

Techs., Inc., 687 F.3d 1377, 1380 (Fed. Cir. 2012). “To be

enabling, the specification of a patent must teach those

skilled in the art how to make and use the full scope of

the claimed invention without undue experimentation.”

Id. (internal quotation marks omitted). “Enablement

serves the dual function in the patent system of ensuring

adequate disclosure of the claimed invention and of

preventing claims broader than the disclosed invention.”

Id. at 1380-81. “Thus, a patentee chooses broad claim

53a

Appendix C

language at the peril of losing any claim that cannot be

enabled across its full scope of coverage.” Id. at 1381. “The

scope of the claims must be less than or equal to the scope

of the enablement to ensure that the public knowledge is

enriched by the patent specification to a degree at least

commensurate with the scope of the claims.” Id. (internal

quotation marks omitted).

“ Whether undue experimentation is needed is

not a single, simple factual determination, but rather

is a conclusion reached by weighing many factual

considerations.” In re Wands, 858 F.2d 731, 737 (Fed.

Cir. 1988). These factors include “(1) the quantity of

experimentation necessary, (2) the amount of direction or

guidance presented, (3) the presence or absence of working

examples, (4) the nature of the invention, (5) the state of

the prior art, (6) the relative skill of those in the art, (7)

the predictability or unpredictability of the art, and (8)

the breadth of the claims.” Id. Although “a specification

need not disclose what is well known in the art,” “[t]ossing

out the mere germ of an idea does not constitute enabling

disclosure.” Genentech, 108 F.3d at 1366. A patent “cannot

simply rely on the knowledge of a person of ordinary skill

to serve as a substitute for the missing information in the

specification.” ALZA Corp. v. Andrx Pharms., LLC, 603

F.3d 935, 941 (Fed. Cir. 2010).

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Appendix C

III. DISCUSSION

A. Written Description

1. Written Description for the Functional

Limitations of Claim 1

Defendants seek summary judgment that the ’180

patent lacks adequate written description for the functional

limitations of claim 1: “(1) the labeled polynucleotide is

hybridized to a nucleic acid sequence of interest, and (2)

. . . the label is detectable when the labeled polynucleotide

is so hybridized.” (D.I. 228 at 6) In Defendants’ view, the

specification does not adequately describe these limitations

because Example V — which, according to Defendants, is

“the only example anywhere in the intrinsic record that

purports to describe the manufacture or synthesis of

a phosphate labeled polynucleotide” — “undisputed[ly]

. . . provides [no] description relating to hybridization or

detectability upon hybridization.” (Id. at 7) Defendants

further contend that Enzo’s technical expert admitted

that the rest of the specification contains “no example,

experiment, or data . . . to suggest that the product of

Example V could hybridize or that its label is detectable

when hybridized.” (Id. at 11; see also D.I. 229-1 Ex. 5 at

131-32)

Enzo responds that “[a] person of ordinary skill

[(‘POSA’)] would have understood” the words “probe”

and “hybridization probe” in the ’180 patent specification

“to (1) be capable of hybridizing and (2) be detectable

upon hybridization.” (D.I. 251 at 4) In Enzo’s view, a

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Appendix C

POSA would have also understood that “hybridization

and detection is the plain purpose to which Example V is

directed.” (Id. at 9) In addition to Example V, Enzo argues

that the specification’s “explicit disclosures of phosphate

attachment[s], labels, linkages, and exemplary chemistry

for making the labeled nucleic acids . . . would have served

as common structural features that allowed [POSAs] to

recognize that the inventors possessed phosphate-labeled

polynucleotides capable of hybridization and subsequent

detection.” (Id. at 10) At oral argument, Enzo additionally

pointed to column 54 line 18 — a portion of the specification

in addition to Example V — as supplying the method for

probes that is “useful for hybridization and detection.” (Tr.

at 95; see also ’180 patent col. 5411. 18-23 (“A particularly

important and useful aspect of the special nucleotides

of this invention is the use of such nucleotides in the

preparation of DNA or RNA probes. Some probes would

contain a nucleotide sequence substantially matching the

DNA or RNA sequence of genetic material to be located

and/or identified.”))

The record demonstrates genuine disputes of material

fact with respect to whether the ’180 patent contains

adequate written description to support the functional

limitations of claim 1. A reasonable jury could find, as

Defendants assert, that neither Example V nor the rest

of the specification “provides any description relating to

hybridization or detectability upon hybridization.” (D.I.

228 at 7) Alternatively, a reasonable jury could instead

find, as Enzo contends, that Example V and/or the rest of

the specification would allow a POSA “to recognize that

the inventors possessed phosphate-labeled polynucleotides

56a

Appendix C

capable of hybridization and subsequent detection.” (D.I.

251 at 10) Hence, the record contains sufficient evidence

from which a reasonable jury could find for either

Defendants or Enzo on written description with respect

to claim 1’s functional limitations. (See, e.g., D.I. 228 at

11; D.I. 229-1 Ex. 5 at 131-32; D.I. 251 at 9-10; ’180 patent

col. 54 11. 18-23)

Accordingly, the Court must deny this portion of

Defendants’ motion for summary judgment.

2. Written Description for Making Internal

Phosphate-Labeled Polynucleotides

Defendants argue that the Court should grant

summary judgment that the specification of the ’180

patent lacks adequate written description for “making

. . . internal phosphate-labeled oligonucleotides” (D.I. 228 at

9) (emphasis omitted); that is, nucleic acids “having a label

positioned internally rather than at the end of the nucleic

acid” (id. at 1). In support of their motion, Defendants note

“[i]t is undisputed that, if the synthesis scheme of Example

V worked at all, it would only succeed in attaching a biotin

to [a] terminal phosphate,” not an internal phosphate. (Id.

at 8) (emphasis omitted) Defendants further contend that,

“[w]ith respect to Example V, Enzo told the Patent Office

that Example V resulted in a terminal label — and not an

internal label.” (Id. at 13) In Defendants’ view, the rest of

the specification similarly lacks an “example, experiment,

or model of any specific species of [an] internal phosphatelabeled polynucleotide.” (Id.)

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Appendix C

Enzo counters that “Example V of the ’180 [p]atent

specification discloses a method that attaches biotin at

phosphate moieties, whether terminal or internal, by

way of the amine groups on biotinylated poly-L-lysine

and biotinyl-1,6-diaminohexane.” (D.I. 251 at 15; see

also D.I. 252 Ex. 9 at A307 (expert testimony)) Enzo

further contends that a POSA “would have been aware

of art showing how to incorporate moieties such as aryl,

alkyl, and methyl phosphonates at internal positions that

would have been understood as suitable chemistry for

likewise incorporating a signaling moiety (and linkage)

at internal positions.” (D.I. 251 at 16; see also D.I. 2521 Ex. 38 at A807-08, 813-14) Thus, in Enzo’s view, “at a

minimum, a dispute of material fact exists as to whether

Example V discloses internal labeling” and whether a

POSA would have been aware of “suitable chemistry

for . . . incorporating a signaling moiety . . . at internal

positions.” (D.I. 251 at 16)

The Court agrees with Enzo that genuine disputes of

material fact preclude summary judgment on this issue.

The parties disagree as to whether Example V discloses a

method that attaches biotin to internal phosphate moieties.

(Compare D.I. 228 at 8, 13 with D.I. 251 at 15) The

parties further disagree on whether a POSA would have

been aware of suitable chemistry for internal labeling.

(Compare D.I. 228 at 17 with D.I. 251 at 16) Both sides

cite record evidence for their contentions, including expert

opinions, such that a reasonable jury could find for either

side: finding insufficient written description for internal

phosphate labeling or, alternatively, adequate written

description for internal phosphate labeling. Therefore,

58a

Appendix C

the record demonstrates genuine disputes of material

fact with respect to whether Example V discloses internal

phosphate labeling and whether the chemistry for internal

phosphate labeling was known in the art.

Accordingly, the Court must deny this portion of

Defendants’ motion for summary judgment.

B. Enablement

Defendants Gen-Probe and Hologic (collectively,

hereinafter, “Hologic”) 5 request that the Court grant

summary judgment that the ’180 patent is invalid for

nonenablement because the specification lacks any

“meaningful disclosure . . . on how to make and use the

vast number of phosphate-labeled polynucleotides covered

by the asserted claims.” (D.I. 222 at 7) In support of its

argument, Hologic points to the following statement in

the ’180 patent about a phosphate-modified nucleotide:

The special nucleotides of this invention include

a phosphoric acid P moiety (also designated

hereinbelow as “PM”), a sugar or monosaccharide

S moiety (also designated hereinbelow as “SM”),

a base B moiety (also designated hereinbelow

as “BASE”), a purine or a pyrimidine and a

signal[]ing chemical moiety Sig covalently

attached thereto, e[it]her to the P, S or B moiety.

(D.I. 222 at 7) (quoting ’180 patent at col. 48 11. 60-66)

5. Gen-Probe became a part of Hologic in August 2012. (D.I.

222 at 1 n.1)

59a

Appendix C

Hologic argues that “[t]he above disclosure does not

indicate . . . any specific nucleotide, any specific label,

any specific linker, any specific position of a phosphatemodified nucleotide within the polynucleotide, or any

specific sequence of length of the polynucleotide.” (D.I.

222 at 7) In Hologic’s view, the rest of the specification

similarly “provides no guidance on how to select, among

numerous possibilities, the sequence and length of the

polynucleotide, the location and number of internal

phosphate labels, or the location and number of nucleotide

analogs.” (Id. at 12)

Hologic further argues that the unpredictability in the

state of the art contributes to rendering the ’180 patent

invalid for nonenablement. (See id. at 8-9, 13-15) Hologic

cites testimony of Enzo’s expert, Dr. Backman, who opined

that, as of the priority date, “it was commonly thought

that . . . chemically labeling the phosphate group would

interfere with hybridization.” (Id. at 8) (internal quotation

marks omitted) Hologic additionally cites the testimony of

one of the ’180 patent inventors, Dr. Stavrianopoulos, who

acknowledged that internal labeling “required methods

and principles of organic chemistry [that were] unknown”

as of the priority date (id. at 14) and remain “difficult

. . . even today” (id. at 10) (internal quotation marks

omitted). In Hologic’s view, making an internal-phosphatepolynucleotide would have also required “extensive

experimentation” because, while “each asserted claim

covers all polynucleotides up to 100,000 DNA nucleotides

long” (id. at 6), yet “the maximum length for chemical

synthesis of a polynucleotide in 1982 was 15 nucleotides”

(id. at 9) (citing Dr. Stavrianopoulos’s testimony).

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Appendix C

Furthermore, according to Hologic, “[t]he synthesis of

a polynucleotide longer than 100,000 nucleotides was not

achieved until 2008.” (Id.)

Enzo responds that “[t]he ’180 [p]atent specification

discloses signaling moieties, . . . provides several examples

of chemical linkages, . . . discloses exemplary lengths of

the claimed polynucleotides (e.g., 5 to 500 nucleotides),

. . . [a]nd . . . discloses that the label is detectable.” (D.I.

247 at 7) In particular, Enzo contends that Example V

“describes a method for attaching biotin at terminal and

internal phosphate moieties of DNA polynucleotides.”

(Id. at 7-8) (“Example V . . . appl[ies] chemistry known in

the art to create an embodiment of the invention”) Enzo

further contends that a POSA attempting to practice the

invention “would not have considered every conceivable

variation” or sequence of the claimed polynucleotide (id.

at 12) (emphasis omitted), because “the specific sequence

of the claimed polynucleotide is . . . no[t] germane to the

claimed inventions” (id. at 1) (emphasis omitted). Finally,

in Enzo’s view, practicing the inventions would have

required, “at most, routine [experimentation],” as the

chemistry for internal labeling “w[as] known in the art”

and a polynucleotide longer than 15 nucleotides “could be

joined together through ligation.” (Id. at 14-15; see also

id. at 6 (“The inventions of the ’180 [p]atent . . . pertain

to nucleic acid hybridization and detection, which was a

decades-old field by the time of the original application

for the ’180 [p]atent.”))

In its reply, Hologic argues that “Enzo’s contention

that . . . claim scope is ‘irrelevant’ . . . turns the enablement

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Appendix C

requirement on its head,” as “[t]he law makes clear that

a specification must enable the full scope of the claimed

invention.” (D.I. 266 at 4) (emphasis omitted) Hologic

notes that “the claims are not limited to the preferred

embodiments” — but, even if they were, “[n]othing in the

[specification] teaches one how to select the length and

sequence of a polynucleotide within the preferred 5 to 500

nucleotides or how to decide where to place the 1 to 100

phosphate-labeled nucleotides within the polynucleotide

of 5-to-500 nucleotides long.” (Id. at 6-7) In Hologic’s

view, the specification also “fails to describe” other

aspects of the invention — for example, a “phosphatelabeled polynucleotide[] that maintain[s] hybridizability

and detectability.” (Id. at 5) Hologic further argues that

Example V “does not describe any actual phosphate

labeling” (id. at 1), does not disclose “the sequence or the

length of the precipitated DNA” (id. at 2), and does not

“indicat[e] whether the reaction is complete or successful”

(id.).

While Enzo asserts that “the missing information

could be found within the knowledge of a skilled artisan,”

Hologic replies that “the specification . . . must supply

the novel aspects of an invention in order to constitute

adequate enablement.” (Id. at 5) (internal quotation marks

omitted) Moreover, even taking into account what a POSA

knew at the pertinent time, that still “fails to show any

actual example of internal phosphate labeling by any

method prior to June 1982.” (Id. at 3) (discussing Dr.

Backman’s testimony; emphasis omitted) Finally, Hologic

disputes Enzo’s assertion that the inventions of the ’180

patent pertain to a “decades-old field.” (D.I. 247 at 6) In

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Appendix C

Hologic’s view, “the field of the claimed invention . . . is

the phosphate labeling of a polynucleotide,” which was

“new” and “highly unpredictable” as of the priority date.

(D.I. 266 at 6) (citing testimony of Dr. Backman, Enzo’s

expert, that “[t]here was ignorance in the art about nonradioactively labeling a nucleic acid probe . . . before [the

priority date]”) (internal emphasis and quotation marks

omitted; first alteration in original)

“To prove that a claim is invalid for lack of enablement,

a challenger must show by clear and convincing evidence

that a person of ordinary skill in the art would not be

able to practice the claimed invention without ‘undue

experimentation.”’ Alcon Research Ltd. v. Barr Labs.,

Inc., 745 F.3d 1180, 1188 (Fed. Cir. 2014) (quoting Wands,

858 F.2d at 736-37). The Court finds that there is no

genuine dispute of fact that the ’180 patent specification

lacks enablement. A reasonable jury simply could not find

for Enzo. Instead, the only conclusion a reasonable jury

could reach is that clear and convincing evidence proves

the ’180 patent is invalid for noneablement.

“[T]he specification must teach those of skill in the art

how to make and how to use the invention as broadly as

it is claimed.” In re Goodman, 11 F.3d 1046, 1050 (Fed.

Cir. 1993) (internal quotation marks omitted; emphasis

added). Here, the claims are extremely broad. Even

limiting claim scope to the preferred embodiments (for

argument’s sake), Hologic correctly points out that the

specification does not teach “one how to select the length

and sequence of a polynucleotide within the preferred 5 to

500 nucleotides or how to decide where to place the 1 to 100

phosphate-labeled nucleotides within the polynucleotide of

63a

Appendix C

5-to-500 nucleotides long.” (D.I. 266 at 7) Moreover, even

if the Court accepts Enzo’s contentions that Example V

discloses internal labeling and that “[t]he inventions of the

’180 patent . . . pertain to . . . hybridization and detection”

(D.I. 247 at 6), neither Example V nor other parts of the

specification indicates whether an internal phosphatelabeled polynucleotide “maintain[s] hybridizability and

detectability” (D.I. 266 at 5; see also generally Genentech,

Inc. v. Novo Nordisk A/S, 108 F.3d 1361, 1366 (Fed.

Cir. 1997) (“Patent protection is granted in return for

an enabling disclosure of an invention, not for vague

intimations of general ideas that may or may not be

workable.”)) As such, again as Hologic explains, a POSA

“would have no choice but to make and test a vast number

of possible variants to the claimed invention.” (D.I. 266

at 7) That is, undue experimentation would be required,

rendering the claims non-enabled.

The Court agrees with Hologic’s comparison of the

present situation to that confronted by the Federal Circuit

in Wyeth v. Abbott Laboratories, 720 F.3d 1380 (Fed. Cir.

2013). In Wyeth, the Federal Circuit affirmed a grant of

summary judgment based on nonenablement. See id. at

1386. Here, “(1) the claims are far broader than in Wyeth,6

(2) the disclosures here are far less than in Wyeth,7 (3) the

6. As Hologic argues, the “millions (or more) of phosphatelabeled polynucleotides with varying sequences and lengths covered

by each asserted claim of the ’180 patent far exceed the tens of

thousands of sirolimus analogs in Wyeth.” (D.I. 222 at 11)

7. As Hologic argues, “[w]hile the specification in Wyeth

disclosed at least one working example of the claimed invention

(sirolimus), the ’180 patent discloses none.” (D.I. 222 at 12)

64a

Appendix C

relevant field is even more unpredictable than in Wyeth,

and (4) the trial-and-error process would have taken even

longer than in Wyeth.” (D.I. 266 at 4) It follows that, here,

as in Wyeth, there is no genuine dispute that the claims

are invalid due to nonenablement.

This same conclusion is supported by consideration

of the Wands factors. See 858 F.2d at 737. Based on

the record, a reasonable factfinder could only find: (1)

the quantity of experimentation necessary to arrive at

embodiments equal to the full scope of the claims is undue;

(2) insufficient direction or guidance is presented in the

patent to allow a POSA to avoid undue experimentation;

(3) insufficient working examples are present; 8 (4)

the invention arises in a field of art that was highly

unpredictable at the time of the invention; (5) the prior

art showed that the pertinent field was unpredictable; (6)

even though the relative skill of those in the art was high,

POSAs at the time did not have sufficient knowledge to

“fill in” all that is missing from the patent; (7) the art was,

as already noted, highly unpredictable; and (8) the claims

are extremely broad. (See D.I. 223-1 Ex. 1 ¶¶ 503-33)

8. Enzo admitted during prosecution of the ’180 patent that

Example V is a “‘paper,’ rather than ‘working example[] . . . .’” (D.I.

223-3 Ex. 17 at ENZO-0096256) In this litigation, Enzo attempts to

create a dispute of fact by pointing to testimony that one inventor

has some recollection of Example V being performed “around ’82,

I don’t remember that now.” (D.I. 250 at A294) Even assuming a

reasonable finder of fact could conclude, on this record, that some

version of Example V was carried out by the inventors, the overall

record remains one on which a reasonable finder of fact could only

find that the claims are not enabled.

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Appendix C

Enzo opposes this conclusion, arguing that “chemistries

. . . known in the art at the relevant time . . . could have

been used to create a polynucleotide” that meets claim

1’s limitations. (D.I. 247 at 14) Enzo’s argument, however,

“ignore[s] the essence of the enablement requirement.”

Genentech, 108 F.3d at 1366. “It is the specification,

not the knowledge of one skilled in the art, that must

supply the novel aspects of an invention in order to

constitute adequate enablement.” Id. “[W]hen there is

no disclosure of any specific starting material or of any

of the conditions under which a process can be carried

out, undue experimentation is required.” Id. Thus, Enzo’s

references as to what “wa[s] known in the art” (D.I. 247

at 14) are unavailing; “a failure to meet the enablement

requirement . . . cannot be rectified by asserting that all

the disclosure related to the process is within the skill of

the art,” Genentech, 108 F.3d at 1366.9

Accordingly, the Court will grant Hologic’s motion

for summary judgment that the ’180 patent is invalid for

nonenablement.10

9. Additionally, even if the Court were to consider Enzo’s

assertions as to the state of the art at the priority date, the record

indisputably establishes that “there was ignorance in the art about

non-radioactively labeling a nucleic acid probe (including nonradioactively labeling any oligo - or polynucleotide in a probe) at a

phosphate moiety before June 23, 1982.” (D.I. 267-1 Ex. 30 at 20)

(emphasis added) Enzo’s assertions, therefore, do not conclusively

establish that the relevant chemistries were “well known in the art”

at the time the ’180 patent was filed. Genentech, 108 F.3d at 1366.

10. The Court recognizes that, during prosecution, Enzo

overcame a nonenablement rejection. (See D.I. 247 at 3-4) (citing

66a

Appendix C

IV. CONCLUSION

For the foregoing reasons, the Court will deny

Defendants’ motion with respect to the written description

requirement and will grant Hologic’s motion with respect

to nonenablement. An appropriate Order follows.

D.I. 250-1 at A583-623, 636-49, 651-58, 660-66, 668-75, 677-83,

685-91, 693-775, 777-84, 786-802, 804-23) However, as Hologic aptly

observes, “the Examiner only considered Enzo’s argument and was

not presented with the overwhelming evidence of nonenablement set

forth in Defendants’ summary judgment briefing.” (D.I 266 at 4 n.4)

67a

APPENDIX D —Appendix

DENIALDOF REHEARING

OF THE UNITED STATES COURT OF APPEALS

FOR THE FEDERAL CIRCUIT,

FILED OCTOBER 29, 2019

NOTE: This order is nonprecedential.

UNITED STATES COURT OF APPEALS

FOR THE FEDERAL CIRCUIT

ENZO LIFE SCIENCES, INC.,

Plaintiff-Appellant

ROCHE MOLECULAR SYSTEMS, INC., ROCHE

DIAGNOSTICS CORPORATION, ROCHE

DIAGNOSTICS OPERATIONS, INC., ROCHE

NIMBLEGEN, INC., BECTON, DICKINSON

AND COMPANY, AKA BECTON DICKSON AND

COMPANY, BECTON DICKINSON DIAGNOSTICS

INC., AKA BECTON DICKSON DIAGNOSTICS,

GENEOHM SCIENCES INC., ABBOTT

LABORATORIES, ABBOTT MOLECULAR, INC.,

Defendants-Appellees

2017-2498, 2017-2499, 2017-2545, 2017-2546

Appeals from the United States District Court for the

District of Delaware in Nos. 1:12-cv-00106-LPS, 1:12-cv00274-LPS, 1:12-cv-00275-LPS, 1:13-cv-00225-LPS, Chief

Judge Leonard P. Stark.

68a

Appendix D

ON PETITION FOR PANEL REHEARING

AND REHEARING EN BANC

Before PROST, Chief Judge, NEWMAN, LOURIE,

DYK, O’MALLEY, REYNA, WALLACH, TARANTO,

CHEN, HUGHES, and STOLL, Circuit Judges*.

PER CURIAM.

ORDER

Appellant Enzo Life Sciences, Inc. filed a combined

petition for panel rehearing and rehearing en banc. A

response to the petition was invited by the court and filed

by Appellees Abbott Laboratories, Abbott Molecular, Inc.,

Becton Dickinson Diagnostics Inc., Becton, Dickinson and

Company, GeneOhm Sciences Inc., Roche Diagnostics

Corporation, Roche Diagnostics Operations, Inc., Roche

Molecular Systems, Inc. and Roche NimbleGen, Inc. The

petition was referred to the panel that heard the appeal,

and thereafter the petition for rehearing en banc was

referred to the circuit judges who are in regular active

service.

Upon consideration thereof,

IT IS ORDERED THAT:

The petition for panel rehearing is denied.

* Circuit Judge Moore did not participate.

69a

Appendix D

The petition for rehearing en banc is denied.

The mandate of the court will issue on November 5,

2019.

FOR THE COURT

October 29, 2019

Date

/s/ Peter R. Marksteiner

Peter R. Marksteiner

Clerk of Court

This is a copy of a public record, reproduced as it was published. It is not legal advice, and it may not be the version a court would rely on. Check the official source before you cite it.