Respondents Brief — Hikma Pharmaceuticals USA Inc., et al., Petitioners v. Vanda Pharmaceuticals Inc.

No. 18-817

IN THE

Supreme Court of the United States

__________

HIKMA PHARMACEUTICALS USA INC., AND WEST-WARD

PHARMACEUTICALS INTERNATIONAL LTD., N/K/A HIKMA

PHARMACEUTICALS INTERNATIONAL LTD.,

Petitioners,

v.

VANDA PHARMACEUTICALS INC.,

Respondent.

__________

ON PETITION FOR A WRIT OF CERTIORARI TO THE

UNITED STATES COURT OF APPEALS

FOR THE FEDERAL CIRCUIT

__________

BRIEF IN OPPOSITION

__________

Nicholas Groombridge

Counsel of Record

Eric Alan Stone

Kira Alexis Davis

Josephine Young

Daniel J. Klein

PAUL, WEISS, RIFKIND, WHARTON

& GARRISON LLP

1285 Avenue of the Americas

New York, NY 10019

(212) 373-3212

ngroombridge@paulweiss.com

FEBRUARY 12, 2019

Counsel for Respondent

QUESTION PRESENTED

Hikma’s Petition wrongly asserts that the

Federal Circuit declared all method-of-treatment

claims to be “automatically” patent-eligible under

Section 101, and asks this Court to decide:

Whether patents that claim a method of

medically treating a patient automatically

satisfy Section 101 of the Patent Act, even if

they apply a natural law using only routine

and conventional steps.

That Question is not presented by the decision

below or any other decision.

ii

PARTIES TO THE PROCEEDINGS

The caption identifies all parties. Petitioners

are Hikma Pharmaceuticals USA Inc., and WestWard Pharmaceuticals International Ltd., N/K/A

Hikma

Pharmaceuticals

International

Ltd.

(together, “Hikma”). The Respondent is Vanda

Pharmaceuticals Inc.

iii

CORPORATE DISCLOSURE STATEMENT

Vanda is publicly traded on the NASDAQ

(symbol: VNDA). No publicly traded entity owns

more than 10% of Vanda’s stock.

iv

TABLE OF CONTENTS

Page

QUESTION PRESENTED ........................................ i

PARTIES TO THE PROCEEDINGS ....................... ii

CORPORATE DISCLOSURE STATEMENT ......... iii

BRIEF IN OPPOSITION ......................................... 1

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

A.

Iloperidone and QTc Prolongation...... 4

B.

Vanda’s Invention and FDA

Approval .............................................. 4

C.

The District Court Proceedings .......... 7

D.

The Federal Circuit Decision .............. 8

REASONS FOR DENYING THE PETITION ......... 9

I. THE FEDERAL CIRCUIT FAITHFULLY

APPLIED—AND ANNOUNCED NO

CATEGORICAL EXEMPTION FROM—THIS

COURT’S SECTION 101 PRECEDENTS .........12

II. THE ’610 PATENT CLAIMS ARE PATENTELIGIBLE UNDER THIS COURT’S

PRECEDENT .....................................................22

v

III.THE DECISION BELOW WILL NOT DELAY

ACCESS TO GENERIC DRUGS OR HARM

SOCIETY ............................................................31

IV. THE PATENT OFFICE HAS NOT CREATED

A CATEGORICAL EXCEPTION FOR

METHODS-OF-TREATMENT TO THIS

COURT’S PRECEDENTS ..................................34

CONCLUSION ........................................................38

vi

TABLE OF AUTHORITIES

CASES

Page(s)

Alice Corp. Pty. v. CLS Bank Int’l,

573 U.S. 208 (2014) .................................... passim

Ass’n for Molecular Pathology v.

Myriad Genetics, Inc.,

569 U.S. 576 (2013) ......................................18, 32

Athena Diagnostics, Inc. v. Mayo

Collaborative Servs., LLC,

No. 2017-2508, 2019 WL 453489

(Fed. Cir. Feb. 6, 2019) .................................20, 21

Bilski v. Kappos,

561 U.S. 593 (2010) ................................13, 15, 28

BSG Tech LLC v. BuySeasons, Inc.,

899 F.3d 1281 (Fed. Cir. 2018).......................... 20

Burnett v. Panasonic Corp.,

741 F. App’x 777 (Fed. Cir. 2018) ..................... 21

Caraco Pharm. Labs., Ltd. v. Novo

Nordisk A/S,

566 U.S. 399 (2012) ........................................... 32

Data Engine Techs. v. Google LLC,

906 F.3d 999 (Fed. Cir. 2018) ........................... 20

Diamond v. Diehr,

450 U.S. 175 (1981) ..........................15, 16, 28, 29

vii

Dolbear v. Am. Bell Tel. Co. (The

Telephone Cases),

126 U.S. 1 (1888) ............................................... 13

In re Downing,

No. 2018-1795, 2018 WL 6436437

(Fed. Cir. Dec. 7, 2018) ...................................... 21

In re Eberra,

730 F. App’x 916 (Fed. Cir. 2018) ..................... 21

Eibel Process Co. v. Minn. & Ont.

Paper Co.,

261 U.S. 45 (1923) ............................................ 14

Erlenbaugh v. U.S.,

409 U.S. 239 (1972) ........................................... 13

Funk Bros. Seed Co. v. Kalo Inoculant

Co.,

333 U.S. 127 (1948) ........................................... 13

Glasswall Sols. Ltd. v. Clearswift Ltd.,

No. 2018-1407, 2018 WL 6720014

(Fed. Cir. Dec. 20, 2018) .................................... 21

Gottschalk v. Benson,

409 U.S. 63 (1972) ............................................ 29

Interval Licensing LLC v. AOL, Inc.,

896 F.3d 1335 (Fed. Cir. 2018).......................... 20

In re Marco Guldenaar Holding B.V.,

911 F.3d 1157 (Fed. Cir. 2018).......................... 20

viii

Mayo Collaborative Servs. v.

Prometheus Labs., Inc.,

566 U.S. 66 (2012) ...................................... passim

Miller v. Bridgeport Brass Co.,

104 U.S. 350 (1881) ........................................... 27

O’Reilly v. Morse,

56 U.S. (15 How.) 62 (1854) .............................. 13

Parker v. Flook,

437 U.S. 584 (1978) .........................14, 15, 28, 29

Praxair Distrib., Inc. v. Mallinckrodt

Hosp. Prods. IP Ltd.,

890 F.3d 1024 (Fed. Cir. 2018).......................... 20

Roche Molecular Sys., Inc. v. Cepheid,

905 F.3d 1363 (Fed. Cir. 2018).......................... 20

SAP Am., Inc. v. InvestPic, LLC,

898 F.3d 1161 (Fed. Cir. 2018).......................... 20

In re Villena,

745 F. App’x 374 (Fed. Cir. 2018) ..................... 21

Voter Verified, Inc. v. Election Sys. &

Software LLC,

887 F.3d 1376 (Fed. Cir. 2018).......................... 21

In re Wang,

737 F. App’x 534 (Fed. Cir. 2018) ..................... 21

STATUTES

21 U.S.C. § 355(b)(1) ............................................... 33

ix

35 U.S.C. § 101................................................. passim

35 U.S.C. § 271(e)(2)(A) ...........................3, 10, 12, 32

35 U.S.C. § 271(e)(2)(C) .....................................12, 33

42 U.S.C. § 262(l)(3)(A) ......................................13, 33

OTHER AUTHORITIES

2019 Revised Patent Subject Matter

Eligibility Guidance,

84 Fed. Reg. 50 (Jan. 7, 2019) ..........11, 35, 36, 37

Sup. Ct. Rule 10 ...................................................... 22

1

BRIEF IN OPPOSITION

I. INTRODUCTION

Hikma’s Petition rests on the premise that the

Federal Circuit “effectively overruled” Mayo

Collaborative Services v. Prometheus Laboratories,

Inc., 566 U.S. 66 (2012) by exempting all method-of-

treatment claims from 35 U.S.C. § 101 scrutiny,

declaring all such claims “automatically” patent

eligible. Pet. at Question Presented.

That premise is wrong. The Federal Circuit did

not announce a categorical rule of patent eligibility

for method-of-treatment patents.

Instead, the Federal Circuit faithfully applied

this Court’s precedents, including Mayo, to just the

’610 patent claims, and held that those claims are

not “directed to” a law of nature itself, but to a

patent-eligible “appl[ication]” of such laws. Alice

Corp. Pty. v. CLS Bank Int’l, 573 U.S. 208, 217

(2014) (citing Mayo, 566 U.S. at 71, 75-79). In

dissent, Chief Judge Prost differed only as to the

outcome of this case, and did not suggest that the

majority was creating a new categorical rule. When

the Federal Circuit denied Hikma’s petition for

review en banc, no judge (including Chief Judge

Prost) dissented from that denial or warned that the

court was trenching on this Court’s decisions. And

the Federal Circuit has considered patent eligibility

in sixteen cases since the panel decision below, and

found claims to be ineligible in fifteen of them.

There is no crisis of patent eligibility at the Federal

Circuit requiring this Court’s review.

2

Nor has the Patent Office run amok by declaring

all methods of treatment eligible for patenting, as

Hikma warns. On the contrary. After Hikma filed

this Petition the Patent Office issued proposed

patent-eligibility guidance that treats the decision

below as just one of many Federal Circuit decisions

implementing—not

overruling—this

Court’s

precedents. The public comment period for that

guidance extends until March of 2019.

This case is therefore a poor vehicle to review

Hikma’s Question Presented, because the decision

below does not present that question and because

these issues are percolating appropriately in the

lower courts and the Patent Office.

This case is also a poor candidate for review on

its facts. The ’610 patent is exactly the kind of

innovation the patent laws are intended to promote.

It covers methods of safely administering one drug,

iloperidone, to treat schizophrenia by administering

specific doses to specified patient populations.

Schizophrenia is a devastating, incurable condition

with few approved treatments. The approved drugs

can have debilitating side effects, and psychiatrists

must often try several before finding one that a

patient can tolerate. Over time, a drug can cease to

work for an individual patient, requiring a switch to

a new one. Iloperidone was an important addition

to their armamentarium, both as another effective

antipsychotic and because it has a markedly lower

risk of a side effect called akathisia, a sense of inner

restlessness so profound that it can induce suicide.

3

The invention of the ’610 patent allowed this

much-needed medicine to come to market. During

early clinical development, certain patients taking

iloperidone developed a potentially fatal cardiac side

effect.

Novartis, which owned the rights to

iloperidone at the time, terminated the development

program. FDA approved iloperidone only after

Vanda’s scientists determined which patients face

that cardiac risk, why they face that risk, and

whether there was any dosage that would be both

safe and effective for those patients.

In the Hatch-Waxman Act, Congress specifically

contemplated that patents like the ’610 patent that

claim “the use of” a molecule would be infringed by

the submission of an Abbreviated New Drug

Application (“ANDA”) seeking approval for a generic

drug.

35 U.S.C. § 271(e)(2)(A).

Generic drug

companies may, of course, argue that those patents

are obvious, or not novel, and that they lack the

required written description of a patent. Hikma

made those arguments, lost at trial, and abandoned

those defenses on appeal. What remains is a casespecific argument that these specific patent claims

were ineligible for patenting under Section 101. The

Federal Circuit’s rejection of that argument

warrants no review in this Court.

The Petition should be denied.

4

STATEMENT OF THE CASE

A. Iloperidone and QTc Prolongation

Iloperidone very nearly did not come to market,

and would not have done so without the invention

claimed by the ’610 patent.

When the pharmaceutical giant Novartis

initially

tried

to

develop

iloperidone

for

schizophrenia, patients began to show a side effect

known as “QTc prolongation.”

The Q and T waves are parts of the cardiac

rhythm—picture two peaks on an EKG—and the

“QTc interval” is the time between them, corrected

(“c”) for the patient’s heart rate. An elongated QTc

interval can cause sudden death.

When QTc

prolongation is observed in a clinical trial, the

pharmaceutical company usually abandons the drug

in development.

That happened here. When iloperidone was

shown to cause QTc prolongation in some patients

and Novartis could not determine the cause or

devise a means to mitigate it, Novartis abandoned

its years of development efforts despite having

already invested hundreds of millions of dollars.

Novartis sold the rights to develop iloperidone to

Vanda in 2004 for just $500,000.

B. Vanda’s Invention and FDA Approval

Vanda’s scientists set out to determine the

causes of iloperidone-induced QTc prolongation,

5

hoping to develop a method for its safe

administration that preserved its efficacy and would

satisfy FDA.

Their efforts proved fruitful. They discovered

that iloperidone and one of its metabolites, known

as P88, inhibited an electric channel in the heart

called the “hERG channel” that could cause

prolongation of the QT interval, while another

iloperidone metabolite, known as P95, did not.

Importantly, and unrelated to their effects on the

heart, iloperidone and P88 are active in the brain in

treating schizophrenia while P95 is not. Vanda’s

scientists also discovered that patients who, because

of a genetic mutation, produce a lower-than-normal

amount of a liver enzyme known as CYP2D6 (socalled “CYP2D6 poor metabolizers”) appeared to be

more at risk of iloperidone-induced QTc

prolongation than patients with normal CYP2D6

metabolic function.

Among other things, the CYP2D6 enzyme is

responsible for breaking down both iloperidone and

P88, and for producing P95. They also found a

correlation between QTc prolongation and the ratio

of P88 to P95 in the blood, and a correlation with

the ratio of (P88+iloperidone) to P95.

They

concluded that a patient with decreased CYP2D6

metabolism will have a substantially higher ratio of

P88 to P95 than would a normal metabolizer, and

can therefore be treated with less iloperidone to

achieve therapeutic efficacy. Separately, because

both P88 and iloperidone create the risk of QTc

prolongation, while P95 does not, a CYP2D6 poor

6

metabolizer would have an increased risk of

iloperidone-induced QTc prolongation given the

same iloperidone dosage that a normal CYP2D6

metabolizer would have.

By combining these several independent

discoveries, Vanda’s scientists were able to

formulate a safe and effective treatment regimen: a

specific dosage range at which a CYP2D6 poor

metabolizer can be effectively treated with

iloperidone without an increased risk of QTc

prolongation.

These discoveries were a breakthrough, and

Vanda succeeded where Novartis had tried and

failed.

The district court found that Vanda’s

successes paved the way to FDA approval: “Vanda

was able to obtain FDA approval for iloperidone

based, at least in part, on the invention disclosed in

the ’610 patent . . . .” App. 4a. Demonstrating the

value of Vanda’s work, Novartis paid Vanda $200

million to re-acquire the rights to iloperidone after

FDA approval, or 400 times what Vanda had paid

Novartis for those rights just five years earlier.

Importantly, the invention of the ’610 patent is

limited to iloperidone. Whether genetic variations

in CYP2D6 efficacy will alter the safety profile or

the efficacy of any other drug depends on many,

drug-specific factors: the extent to which the drug is

processed by CYP2D6, whether other metabolic

pathways will compensate for poor CYP2D6

metabolism, and whether the resulting metabolites

will have effects similar to, stronger than, or weaker

than the original drug. 1 C.A. App. 7216-7217.

7

C. The District Court Proceedings

After FDA approved iloperidone for the

treatment of schizophrenia, Hikma’s predecessor

filed an Abbreviated New Drug Application seeking

FDA-approval to sell iloperidone. Vanda sued,

asserting the ’610 patent and the now-expired

patent on the iloperidone molecule.

The district court presided over a five-day bench

trial, after which it found the asserted claims of the

’610 patent infringed, non-obvious, not invalid for

lack of written description, and not invalid for lack

of patent-eligible subject matter. App. 69a-90a.

As relevant here, the district court found that

under Step One of this Court’s Section 101 test, the

claims of the ’610 patent “depend upon laws of

nature,” but that under Step Two “the process of

using . . . genetic test[s] to inform the dosage

adjustment recited in the claims was not routine or

conventional . . . .” App. 76a-78a.

Notably,

Hikma

presented

law-of-nature

arguments in the district court that it then

abandoned. Initially, Hikma posited a supposed

natural law that “where a patient poorly

metabolizes a drug, the patient should receive less

drug.” 1 C.A. App. 7323-7324. Hikma abandoned

that because it is wrong as a matter of science; for

some drugs, poor metabolizers should receive higher

doses, not lower doses. Id. at 7323. Then Hikma

suggested that the natural law is that “the more

iloperidone you have in your system the higher the

side effects would be.” Id. That, too, is wrong; some

8

iloperidone side-effects are not dose-dependent at

all. Id. at 7323-7324.

D. The Federal Circuit Decision

At the Federal Circuit, Hikma posited yet

another natural law: that “the asserted claims are

directed to a natural relationship between

iloperidone,

CYP2D6

metabolism,

and

QT

prolongation.” C.A. Dkt. No. 24 at 47.

The Federal Circuit exhaustively examined this

Court’s patent-eligibility precedents. The majority

opinion held that the ’610 patent claims—unlike the

diagnostic-method claims in Mayo—are not

“directed to” a law of nature, but to a concrete

method of treating specific patients with specific

dosages:

At bottom, the claims here are directed to a

specific method of treatment for specific

patients using a specific compound at specific

doses to achieve a specific outcome. They are

different from Mayo. They recite more than

the natural relationship between CYP2D6

metabolizer genotype and the risk of QTc

prolongation.

App. 35a. “Thus, the ’610 patent claims are ‘a new

way of using an existing drug’ that is safer for

patients because it reduces the risk of QTc

prolongation.” App. 32a.

Chief Judge Prost dissented, and would have

held that these claims are ineligible for patenting.

9

Notably, the dissent did not suggest that the

majority was creating any new categorical rule for

method-of-treatment claims.

Chief Judge Prost

simply would have reached a different outcome in

this case. And it was central to the dissent that the

use of iloperidone to treat schizophrenia “long

predated the ’610 patent,” as in Mayo where the

thiopurine drugs were in use long before the Mayo

patent. App. 47a-48a. Respectfully, the undisputed

record evidence contradicted that premise: The

priority date of the ’610 patent is five years before

FDA approved iloperidone, and thus physicians did

not use iloperidone to treat schizophrenia “long” (or,

at all) before the ’610 patent.

Hikma sought en banc review. The Federal

Circuit denied that request, without dissent. App.

93a-94a.

REASONS FOR DENYING THE PETITION

Hikma’s petition rests on the false premise that

the Federal Circuit held that all method-oftreatment patent claims are “automatically” eligible

for patenting under Section 101, see Pet. at

Question Presented, supposedly overruling this

Court’s Section 101 precedents.

The Federal Circuit did not exempt method-oftreatment claims from Section 101 scrutiny.

Instead, as Vanda shows below in Section I, the

Federal Circuit exhaustively reviewed this Court’s

Section 101 decisions and sought to apply them to

the facts of only this case. It made no statements

10

announcing a broad exemption for all method-oftreatment patents.

And as Vanda shows below in Section II, the

majority opinion was correct on the merits. The ’610

patent claims are exactly the type of claims that are

patent-eligible under Section 101. Unlike the claims

in Mayo, these claims do not simply describe a

natural relationship in the human body and tell

doctors to consider whether a dosage adjustment is

indicated. The ’610 patent claims require doctors to

give specific dosages of iloperidone to specific

patient populations. That the inventors discovered

the physiological processes that make the dosages

safe and effective does not convert their patent into

a monopolization of the underlying physiological

processes themselves. The scientific discoveries

disclosed in the patent are available to all.

Hikma’s and its amici’s fears of a sea change if

the Federal Circuit’s decision is not reversed are

unfounded, as Vanda shows in Section III. Hikma

warns that drug companies will now list more

method-of-treatment patents in the FDA’s Orange

Book and thereby improperly obtain 30-month stays

of FDA approval for generic drugs. But Congress

specifically

contemplated

that

method-of-use

patents would be infringed by the submission of a

generic’s ANDA, see 35 U.S.C. § 271(e)(2)(A), drug

companies are already required to list method-oftreatment patents in the Orange Book, and

thousands of method-of-treatment patents are

already listed.

11

Hikma’s and its amici’s purported concerns

reveal what is really at stake here: The genericdrug industry wants this Court to hold that all

method-of-treatment patents are ineligible under

Section 101 because they depend on the body’s

physiological response to a foreign substance. That

would defy this Court’s recognition that a “new way

of using an existing drug” could be patent-eligible.

Mayo, 566 U.S. at 87. And it would defy Congress’s

intent to make submission of an ANDA an act of

infringement of method-of-use patents.

Finally, Hikma’s and its amici’s stated concerns

about the Patent Office are also misplaced, as

Vanda shows in Section IV. The Patent Office

memorandum on which Hikma relies says only that

method-of-treatment claims that “apply” natural

relationships, “as opposed to being ‘directed to’

them,” are eligible for patenting.

App. 98a

(emphasis in original).

Since Hikma filed its

Petition, the Patent Office has promulgated new

proposed Section 101 rules, and they say nothing

about an exemption for all method-of-treatment

claims.

2019 Revised Patent Subject Matter

Eligibility Guidance, 84 Fed. Reg. 50 (Jan. 7, 2019).

In sum, everything is percolating in the lower

courts as this Court instructed. Certiorari is not

warranted.

12

I.

THE FEDERAL CIRCUIT FAITHFULLY

APPLIED—AND ANNOUNCED NO

CATEGORICAL EXEMPTION FROM—THIS

COURT’S SECTION 101 PRECEDENTS

This Court’s Section 101 precedents distinguish

between (i) patents that are “directed to” (that is,

they seek to monopolize) laws of nature, which may

not be eligible for patenting, and (ii) patents that

simply apply laws of nature (which nearly all

patents do), and which pose no eligibility concerns.

The distinction between claims that seek to

monopolize laws of nature and claims that apply

such laws reverberates through the Court’s latetwentieth-century Section 101 jurisprudence and

supports the two-step test of Alice and Mayo. See

Alice, 573 U.S. at 217; Mayo 566 U.S. at 75-79.

1. That method-of-treatment claims may be

patented is clear from Section 101 itself. The Patent

Act begins by declaring that claims to a “process”—

that is, method claims—are patentable:

Whoever invents or discovers any new and

useful process, machine, manufacture, or

composition of matter, or any new and useful

improvement thereof, may obtain a patent

therefor, subject to the conditions and

requirements of this title.

35 U.S.C. § 101 (emphasis added). Among the

patentable processes are uses of drugs for therapy;

those patents are specifically called out for inclusion

in patent litigation over both generic drugs and

biosimilars. See 35 U.S.C. § 271(e)(2)(A), (e)(2)(C);

13

42 U.S.C. § 262(l)(3)(A). All of these provisions

must be read in pari materia. See Erlenbaugh v.

U.S., 409 U.S. 239, 243-44 (1972).

To be sure, this Court has held that despite the

facial breadth of Section 101, one cannot patent, and

thus monopolize, naturally occurring phenomena,

because they are not “new,” Bilski v. Kappos, 561

U.S. 593, 602 (2010), and one cannot patent, and

thus monopolize, fundamental laws of nature or

abstract ideas, which are concepts that should be

reserved for “the storehouse of knowledge of all

men,” Funk Brothers Seed Co. v. Kalo Inoculant Co.,

333 U.S. 127, 130 (1948).

Courts must “tread carefully in construing this

exclusionary principle,” however, “lest it swallow all

of patent law.” Alice, 573 U.S. at 217. That is

because, “[a]t some level, ‘all inventions . . . embody,

use, reflect, rest upon, or apply laws of nature,

natural phenomena, or abstract ideas.’” Id. (quoting

Mayo, 566 U.S. at 71).

To take a classic example, while Samuel Morse

could not patent, and thus monopolize, the innate

power of electro-magnetism to send messages at a

distance (which Hikma highlights, Pet. at 6), he

could patent the telegraph machines that depended

on that innate power (which Hikma omits). See

Dolbear v. Am. Bell Tel. Co. (The Telephone Cases),

126 U.S. 1, 534 (1888); O’Reilly v. Morse, 56 U.S. (15

How.) 62 (1854).

2. The distinction between patents “directed to”

laws of nature and patents that merely apply those

14

natural laws reverberated through the Court’s latetwentieth-century Section 101 cases.

In Parker v. Flook, on which Hikma focuses, the

patent was directed to a method for updating

numerical “alarm limits” during petrochemical and

oil-refining catalytic-conversion processes, but the

“only novel feature of the method” was the

“mathematical formula” itself. 437 U.S. 584, 585

(1978). 1 The patent did not “purport to contain any

disclosure relating to the chemical processes at

work, the monitoring of process variables, or the

means of setting of an alarm or adjusting an alarm

system.” Id. at 586. And it did not “purport to

explain how to select the appropriate margin of

safety, the weighting factor, or any of the other

variables.” Id. The Court analogized the claims to a

patent on applying the formula for “determining the

circumference of a wheel” or on the Pythagorean

theorem, with “a final step indicating that the

formula, when solved, could be usefully applied to

existing surveying techniques.” Id. at 590, 595.

Such a patent would be directed to, and monopolize,

the law of nature itself.

On the other hand, the Court stressed that “it is

equally clear that a process is not unpatentable

simply because it contains a law of nature or a

mathematical algorithm.”

437 U.S. at 590

(emphasis added) (citing Eibel Process Co. v. Minn.

& Ont. Paper Co., 261 U.S. 45 (1923)). The claim in

Hikma chides the Federal Circuit for not citing Flook.

Pet. at 19. Neither party relied on Flook in the lower courts, or

cited it other than in passing.

1

15

Eibel Process was to “an improvement on a

papermaking machine that made use of the law of

gravity.” Flook, 437 U.S. at 590 n.12. A claim that

merely relies on the actions of, but does not attempt

to monopolize, a law of nature is eligible for

patenting; what is ineligible, the Court held, is a

patent claim “directed essentially to” an ineligible

concept. Flook, 437 U.S. at 595 (emphasis added).

“Very simply, our holding today is that a claim for

an improved method of calculation, even when tied

to a specific end use, is unpatentable subject matter

under § 101.” Id. at 595 n.18 (emphasis added).

This Court’s subsequent decision in Diamond v.

Diehr, 450 U.S. 175 (1981), “established a limitation

on the principles articulated in Benson and Flook.”

Bilski, 561 U.S. at 611. As in Flook, the claims in

Diehr covered the computerized use of a well-known

mathematical formula in a method of molding

rubber under heat and pressure. 450 U.S. at 17778. The Court reasoned that the patentee did not

“seek to patent a mathematical formula” itself, but

rather an industrial process for the molding of

rubber products. Id. at 187. While the process

“employ[ed] a well-known mathematical equation,”

the patent would not “pre-empt the use of that

equation,” but only prohibit others from using that

equation “in conjunction with all of the other steps

in [the] claimed process.” Id. The Court found the

claims patent-eligible.

3. The “opposite conclusions” reached in Flook

and Diehr, Mayo, 566 U.S. at 80, are at the heart of

the Court’s modern Section 101 decisions. In Alice,

16

the Court explained that the essence of the claims in

Flook was a monopolization of the mathematical

formula itself when deployed on a computer, while

“the claims in Diehr were patent eligible because

they improved an existing technological process.”

573 U.S. at 223. And in Mayo the Court explained

that the patent was upheld in Diehr “because of the

way the additional steps of the process integrated

the equation into the process as a whole.” 566 U.S.

at 80.

Relying on Flook and Diehr, the Court’s decisions

in Alice and Mayo set out the modern, two-step test

for determining patent eligibility.

At Step One, “we determine whether the claims

at issue are directed to one of those patent-ineligible

concepts.” Alice, 573 U.S. at 217 (citing Mayo, 566

U.S. at 75-79) (emphasis added). If the claim is not

directed to an ineligible concept, it is eligible for

patenting.

If the claim is “directed to” an ineligible concept,

at Step Two “we then ask, ‘what else is there in the

claims before us.’” Alice, 573 U.S. at 217. “To

answer that question,” a court considers the claim

elements individually and as an ordered

combination, to determine whether the elements

beyond the claimed law of nature “‘transform the

nature of the claim’ into a patent-eligible

application” of that law of nature. Id. (quoting

Mayo, 566 U.S. at 78). The Court has described this

as a search for “an inventive concept.” Alice, 573

U.S. at 217.

17

Hikma’s Question Presented asserts that

method-of-treatment claims that “apply” natural

laws fail Step One, and that their patent eligibility

must be determined at Step Two. See Pet. at

Question Presented. Hikma misreads Alice and

Mayo. If merely “apply[ing]” a natural law caused a

claim to fail Step One, the “exclusionary principle”

of those cases could “swallow all of patent law,”

Alice, 573 U.S. at 217 (citing Mayo, 566 U.S. at 71),

and the Alice/Mayo test would collapse down into

only Step Two. That is because, as the Court

warned in Alice and Mayo, “[a]t some level, ‘all

inventions . . . apply laws of nature . . . .’” Alice, 573

U.S. at 217 (quoting Mayo, 566 U.S. at 71)

(emphases added).

At Step One, then, a court may not merely

determine whether the claim applies or relies on

laws of nature—the answer to which would

essentially always be “yes”—but must instead

determine whether a patent claim is “directed to” a

patent-ineligible concept. Alice, 573 U.S. at 217

(emphasis added).

The claims in Alice were directed to the abstract

idea of an intermediated settlement, “a fundamental

economic practice long prevalent in our system of

commerce,” id. at 219 (citation and internal

quotation marks omitted), and sought to monopolize

computerized implementation of that abstract idea.

Further scrutiny at Step Two was therefore needed.

Likewise, in Mayo, the diagnostic claims were

directed to laws of nature, specifying and purporting

to monopolize “relationships between concentrations

18

of certain metabolites in the blood and the likelihood

that a dosage of a thiopurine drug will prove

ineffective or cause harm.” Mayo, 566 U.S. at 77.

Critically, the claims did not require the doctor to

perform any particular treatment; infringement

occurred merely from the doctor’s measuring the

metabolites and considering the results. Id. at 8687. A doctor would infringe Mayo’s patent even if

the “subsequent treatment decision” does not

“change in light of the inference he has drawn using

the correlations” described in the patent. Id. Step

Two scrutiny was therefore required.

Nothing in those cases, however, suggests—as

Hikma would have it—that Step Two scrutiny is

required any time a claim applies a law of nature.

On the contrary, the Court noted that the Mayo

diagnosis claims were unlike “a typical patent on a

new drug or a new way of using an existing drug,”

which “confine their reach to particular applications

of” natural laws. 566 U.S. at 87 (emphases added).

And while the Court later invalidated as patentineligible claims to naturally occurring DNA

sequences, the Court again noted that claims to

natural phenomena themselves are different than

“method claims” and claims on “new applications of

knowledge about” the claimed DNA sequences.

Ass’n for Molecular Pathology v. Myriad Genetics,

Inc., 569 U.S. 576, 595-96 (2013) (italics in original).

4. The Federal Circuit faithfully applied this

Court’s Section 101 precedents.

19

Far from “effectively overrul[ing]” Mayo, as

Hikma contends, see Pet. at 1, the Federal Circuit

cited Mayo on every page of its Section 101 analysis

and sought to apply Mayo, Alice, and Myriad to the

facts of this case. And far from “exempt[ing]”

method-of-treatment claims from the Section 101

analysis, see Pet. at Question Presented, the

Federal Circuit limited its discussion to the ’610

patent.

Vanda discusses the merits of that decision

further in Section II below, but what matters here is

that the Federal Circuit did not purport to announce

a categorical rule for all method-of-treatment

patents. Central to its resolution of this case was

that the claims here “are directed to a specific

method of treatment for specific patients using a

specific compound at specific doses to achieve a

specific outcome.” App. 35a. The court contrasted

that specificity with “the claim at issue in Mayo,”

and concluded that, as foreshadowed by Mayo, “the

’610 patent claims are ‘a new way of using an

existing drug’ that is safer for patients because it

reduces the risk of QTc prolongation.” App. 32a

(quoting Mayo, 566 U.S. at 87). And unlike the

claims in Mayo, which this Court found were

“directed to” a law of nature itself, the Federal

Circuit found that the ’610 patent does not “claim”—

and thus seek to monopolize—“the relationships

between iloperidone, CYP2D6 metabolism, and QTc

prolongation,” but rather claims only “an application

of that relationship.” App. 32a (emphasis added).

20

Chief Judge Prost’s dissent, too, was about only

the ’610 patent. The dissent did not suggest that

the majority was enacting a categorical rule, or

overruling Mayo, or otherwise systematically

flouting this Court’s decisions. When the Federal

Circuit denied Hikma’s request for en banc review,

no member of that court dissented from that denial

or suggested that the Vanda decision effected a sub

silentio overruling of this Court’s cases.

The Federal Circuit’s subsequent decisions

confirm its fidelity to this Court’s jurisprudence.

The Federal Circuit has addressed Section 101 in

sixteen decisions since the panel decision below, and

it held patent claims to be ineligible in fifteen of

them. 2 In the most recent such decision, the

See Athena Diagnostics, Inc. v. Mayo Collaborative

Servs., LLC, No. 2017-2508, 2019 WL 453489 (Fed. Cir. Feb. 6,

2

2019) (invalid claim to natural law; method of diagnosing a

neurological disorder); In re Marco Guldenaar Holding B.V.,

911 F.3d 1157 (Fed. Cir. 2018) (invalid claim to abstract idea;

rules for playing games); Data Engine Techs. v. Google LLC,

906 F.3d 999 (Fed. Cir. 2018) (invalid claim to abstract idea;

methods of tracking data changes in a spreadsheet); Roche

Molecular Sys., Inc. v. Cepheid, 905 F.3d 1363 (Fed. Cir. 2018)

(invalid claim to natural phenomenon; method for detecting

pathogenic bacterium); BSG Tech LLC v. BuySeasons, Inc.,

899 F.3d 1281 (Fed. Cir. 2018) (invalid claim to abstract idea;

methods for indexing information); SAP Am., Inc. v. InvestPic,

LLC, 898 F.3d 1161 (Fed. Cir. 2018) (invalid claim to abstract

idea; methods of calculating, analyzing, and displaying

investment data); Interval Licensing LLC v. AOL, Inc., 896

F.3d 1335 (Fed. Cir. 2018) (invalid claim to abstract idea; nonoverlapping onscreen presentation of two sets of information);

Praxair Distrib., Inc. v. Mallinckrodt Hosp. Prods. IP Ltd., 890

F.3d 1024 (Fed. Cir. 2018) (invalid claim to printed matter;

method for providing prescribing information relating to a

21

Federal Circuit described the Vanda decision not as

a categorical watershed for method-of-treatment

claims, but simply as a decision about the facts of

this case: “holding that method of treatment by

administering drug at certain dosage ranges based

on a patient’s genotype was not directed to a natural

law.” Athena, 2019 WL 453489, at *6. 3

Far from unleashing a flood of pro-patentee

Section 101 decisions, the Vanda decision is just one

case in a pattern of decisions faithfully applying this

Court’s Alice/Mayo precedent.

harmful side effect); Voter Verified, Inc. v. Election Sys. &

Software LLC, 887 F.3d 1376 (Fed. Cir. 2018) (invalid claim to

abstract idea; methods for self-verifying); see also Glasswall

Sols. Ltd. v. Clearswift Ltd., No. 2018-1407, 2018 WL 6720014

(Fed. Cir. Dec. 20, 2018) (invalid claim to abstract idea;

filtering of electronic files and data); In re Downing, No. 20181795, 2018 WL 6436437 (Fed. Cir. Dec. 7, 2018) (invalid claim

to abstract idea; creating an electronic spreadsheet for

personal management); In re Villena, 745 F. App’x 374 (Fed.

Cir. 2018) (invalid claim to abstract idea; property valuation);

Burnett v. Panasonic Corp., 741 F. App’x 777 (Fed. Cir. 2018)

(invalid claim to abstract idea; converting geospatial

coordinates into natural numbers); In re Wang, 737 F. App’x

534 (Fed. Cir. 2018) (invalid claim to abstract idea; phonetic

symbol system); In re Eberra, 730 F. App’x 916 (Fed. Cir. 2018)

(invalid claim to abstract idea; product promotion).

The Athena case shows that Section 101 issues are

percolating in the academy as well as the lower courts.

Hikma’s amici include law professors. But in Athena, ten

other law professors urged that the claims were patenteligible. Brief of Amici Curiae Ten Law Professors (Nov. 13,

2017), ECF No. 54.

3

22

II.

THE ’610 PATENT CLAIMS ARE PATENTELIGIBLE UNDER THIS COURT’S

PRECEDENT

A writ of certiorari is rarely appropriate to

correct “erroneous factual findings or the

misapplication of a properly stated rule of law” (Sup.

Ct. Rule 10), but here the writ is even less

appropriate because the Federal Circuit made no

erroneous finding of fact or conclusion of law. On

the contrary, the claims of the ’610 patent are

exactly the type of innovation that the Patent Act

encourages and rewards.

1. The ’610 patent inventors’ work paved the

way for FDA to approve iloperidone. Thus, while

Hikma characterizes the ’610 patent claims as “the

administration of a known drug for a known use,”

Pet. 20, 37; accord Amicus Br. of The Association for

Accessible Medicines, et al. (“Inventia Br.”) at 14-15

& n.14), the undisputed evidence belies that

characterization.

Iloperidone was not approved for use at all before

the invention of the ’610 patent.

Instead,

iloperidone’s tendency to induce QTc prolongation

stalled its commercial development. Novartis—the

world’s fourth largest pharmaceutical company by

annual revenue ($52.54 billion in 2017)—could not

solve the QTc problem. It abandoned iloperidone

and sold the rights to the pharmaceutical compound

to Vanda for $500,000. Through the invention of the

’610 patent, Vanda satisfied FDA that iloperidone

could safely treat CYP2D6 poor metabolizers.

Novartis then repurchased the rights from Vanda,

23

at a price 400 times higher than what Vanda paid

Novartis just a few years earlier.

The district court found that Vanda obtained

FDA approval for iloperidone “at least in part”

because of the ’610 patent’s claimed method of

reducing “the side effects associated with QTc

prolongation in order to safely treat patients

suffering from schizophrenia.”

App. 72a-73a.

Hikma did not challenge that finding on appeal. 4

2. The ’610 patent inventors’ scientific analysis

and inventive application of their findings is exactly

the type of work that the patent laws should protect.

They studied genetics, liver metabolism, cardiac

electrical channels, and brain activity to find a safe

way to treat specific psychiatric conditions with a

specific compound at specified doses. They then

patented only the specific method of treatment they

developed, not the underlying natural processes.

When the inventors began their work, much was

unknown.

No one knew why iloperidone was

4 Inventia—which purports to be a friend of the Court but

has also been sued by Vanda under this very patent—asserts

that the appropriate iloperidone dose for a CYP2D6 poor

metabolizer was in the prior art, relying on the Jain reference.

(Inventia Br. at 14-15 & n.14). That is incorrect. In allowing

the ’610 patent claims, the Patent Office noted that none of the

prior art, including Jain, taught or suggested adjusting the

dosage “based on a determination of the presence or absence of

a CYP2D6 poor metabolizer genotype.” 1 C.A. App. 2877.

Indeed, Jain completely missed that some patients taking 24

mg/day of iloperidone were at risk of serious cardiac

complications. The ’610 inventors solved a problem that Jain

overlooked.

24

associated with QTc prolongation. For example,

some people are genetically predisposed to have

elongated QTc intervals, and the QTc prolongation

seen when administering iloperidone might have

had nothing to do with iloperidone at all. Or the

QTc prolongation could have had something to do

with the body’s metabolism of iloperidone, and been

caused by iloperidone itself, or one or some of its

many metabolites.

By studying iloperidone metabolism and data

about genetic mutations seen in some patients

taking iloperidone, the ’610 patent inventors

determined that QTc prolongation was more

prevalent in CYP2D6 poor metabolizers given

iloperidone.

The district court found that at the time of the

’610 patent invention, it was not known how the

CYP2D6 enzyme metabolized iloperidone, or the

effects on the body of the resulting metabolites.

Rather, it was known that some CYP2D6metabolized drugs should be given in higher doses

to CYP2D6 poor metabolizers, while others should

be given in lower doses, while still others should not

be given to CYP2D6 poor metabolizers at all. App.

72a.

The ’610 patent inventors learned that

iloperidone itself and a metabolite of iloperidone

called P88 each have anti-schizophrenic effects in

the brain and each also inhibit the heart’s hERG

channel, which can result in elongated QTc

intervals.

They also learned that the enzyme

CYP2D6 plays two roles in the metabolism of

25

iloperidone: it results in a metabolite called P95,

which is not active in the brain and which also does

not inhibit the hERG channel in the heart, and it

breaks down the other significant metabolite, P88.

The inventors then realized that both antischizophrenic efficacy and the risk of QTc

prolongation depend on the ratio in the patient’s

blood of iloperidone to P95, and on the ratio of

(iloperidone+P88) to P95. A person with diminished

CYP2D6 functionality (i) needs less iloperidone to

achieve anti-schizophrenic efficacy, and (ii) is at an

increased

risk

of

iloperidone-induced

QTc

prolongation, because she has more iloperidone and

P88 and less P95 in her blood than a patient with

normal CYP2D6 functionality.

Using this

knowledge, the inventors determined that CYP2D6

poor metabolizers could be treated both safely and

efficaciously with a dose of 12 mg/day or less of

iloperidone, where normal metabolizers could be

safely and efficaciously treated with a dose of more

than 12 mg/day and up to 24 mg/day.

3. Hikma contends that this was all just the

discovery of a “natural law,” namely that “a risk of

QTc prolongation for a patient having a CYP2D6

poor metabolizer genotype is lower following the

internal administration of 12 mg/day or less.” Pet.

at 11-12.

If the manner in which a specific drug is

metabolized by a specific enzyme is a “natural law,”

then the invention of the ’610 patent is a practical

application of not one natural law but of at least

26

seven such laws, spanning four discrete parts of the

body:

In the Brain

•

Iloperidone and P88 bind to neurological

receptors, giving iloperidone its efficacy as a

schizophrenia treatment.

•

P95 does not bind to those neurological

receptors.

In the Heart

•

Iloperidone and P88 inhibit the cardiac hERG

channel, creating a QTc prolongation risk.

•

P95 does not inhibit the hERG channel.

In the Liver

•

Metabolism of iloperidone through

CYP2D6 enzyme results in P95.

•

CYP2D6 degrades P88.

the

In the Patient’s Genome

•

Some people have genetic mutations that

result in decreased CYP2D6 functionality.

What is notable about these “natural laws” is

that the ’610 patent does not claim any of them, as

the Federal Circuit found.

“The inventors

recognized the relationships between iloperidone,

CYP2D6 metabolism, and QTc prolongation, but

27

that is not what they claimed. They claimed an

application of that relationship.”

App. 32a

(emphases added).

And the specification of the ’610 patent recites

every one of these scientific discoveries about

iloperidone metabolism, safety, and efficacy. 5 By

disclosing those scientific discoveries but not

claiming them, the ’610 patent inventors dedicated

those discoveries to the public. See, e.g., Miller v.

Bridgeport Brass Co., 104 U.S. 350, 352 (1881).

For example, scientists or doctors or lawyers can

use the knowledge that P88 inhibits the hERG

channel however they wish. They can use the

knowledge that CYP2D6 degrades P88. They can

investigate whether similar metabolic pathways and

genetic mutations combine to create a risk of QTc

prolongation for a compound other than iloperidone.

They can even develop a method of dosing

iloperidone itself to reduce the risk of QTc

5 The ’610 patent specification discloses that iloperidone is

active in the brain to treat schizophrenia and that P88 has a

similar “pharmacological profile,” see 1 C.A. App. 38, 44 (’610

patent, col. 1, ll. 34-47; col. 13, ll. 15-22); that P95 is viewed as

“pharmacologically inactive,” see id. at 39 (’610 patent, col. 4,

ll. 49-53); that iloperidone and P88 activate the hERG channel,

see id. (’610 patent, col. 4, ll. 37-53); that P95 does not activate

the hERG channel, id.; that CYP2D6-induced metabolism of

iloperidone results in P95; that CYP2D6 degrades P88, see id.

at 40 (’610 patent, col. 6, ll. 57-59); and that a person’s genetic

profile can dictate her CYP2D6 enzymatic functionality,

including the relative concentrations of P88 and P95 in

patients given iloperidone, see id. at 40-41 (’610 patent, col. 6,

l. 54 to col. 8, l. 31).

28

prolongation that is different than the methods

claimed by the ’610 patent.

The ’610 patent claims only a specific application

of its inventors’ work: treating a patient with

schizophrenia using iloperidone by determining,

through a genotyping test, whether the patient is

genetically predisposed to CYP2D6 poor metabolism

and then administering one of two specified doses of

iloperidone depending on the results of that test.

Contrary to Hikma’s argument, Flook does not

mean that these treatment elements are mere “postsolution activity.” In fact, Flook provides a useful

contrast. In explaining what kind of claim would

add insignificant post-solution activity to an

ineligible concept, Flook stated that “the

Pythagorean theorem would not have been

patentable, or partially patentable, because a patent

application contained a final step indicating that the

formula, when solved, could be usefully applied to

existing surveying techniques.” 437 U.S. at 590; see

also Diehr, 450 U.S. at 191-92 (explaining Flook’s

holding as rendering “insignificant post-solution

activity” impermissible (emphasis added)); accord

Bilski, 561 U.S. at 610-11. By comparison, the

concrete elements of the ’610 patent claims

requiring the administration of specific dosages of

iloperidone to specific subpopulations of patients

was part of, and necessary to, accomplishing the

solution provided by the claims: the relative risk

reduction of iloperidone-induced QTc prolongation.

The treatment elements are neither “insignificant”

nor “post-solution.” They are critical to the utility of

29

the claimed method and intertwined throughout the

method of treatment itself.

4. The ’610 patent claims are therefore like the

claims in Diehr and Eibel Process: “an application of

a law of nature or mathematical formula” to a

previously unknown and unavailable treatment and

thus “deserving of patent protection.” Diehr, 450

U.S. at 187 (emphasis in original). Unlike in Flook,

the ’610 patent claims are not “directed essentially

to” a law of nature. Flook, 437 U.S. at 595. The

claims pose no risk of “tying up the use of the

underlying natural laws, inhibiting their use in the

making of further discoveries,” Mayo, 566 U.S. at

73, but foreclose others from their use only “in

conjunction with all of the other steps of the[]

claimed process[es],” Diehr, 450 U.S. at 187. Their

“substantial practical application” is not for carrying

out any particular law of nature, Gottschalk v.

Benson, 409 U.S. 63, 71-72 (1972), but to a “new

way of using an existing drug,” Mayo, 566 U.S. at

87, one that allowed the drug to be legally

prescribed in the United States.

Hikma’s Petition demonstrates this graphically.

In its chart, Pet. at 34-35, Hikma compares the

elements of the Mayo claims to claim 1 of the ’610

patent. Notably, even Hikma finds no analogue in

the Mayo patent to the dosage step in the ’610

patent. See Pet. at 35. That is exactly right. The

diagnostic method in Mayo did not require the

doctor to do anything based on the observed

metabolite levels, and the Mayo inventors did not

invent or determine an appropriate dosage for a

30

drug or any other treatment step based on the

diagnostic inquiry. What they sought to patent, this

Court held, was the natural relationship among the

metabolites itself. Hikma makes much of the fact

that the Mayo claims “covered the administration of

a specific drug (thiopurine),” Pet. at 8, but that

administration was simply a prerequisite to being

able to claim the observation of the relationship of

the thiopurine metabolites. Mayo, 566 U.S. at 77

(“While it takes a human action (the administration

of a thiopurine drug) to trigger a manifestation of

this relation in a particular person, the relation

itself exists in principle apart from any human

action.”). In deciding that this case “is not Mayo”

App. 31a, and that the claims here are not “directed

to” a law of nature at Step One of the Alice/Mayo

test, the Federal Circuit committed no error.

5. Finally, much of Hikma’s Petition argues that

the steps of the ’610 patent are “routine and

conventional” uses of a law of nature. That is the

Step Two inquiry of the Alice/Mayo framework, and

therefore has no bearing on the Question Presented,

which addresses only whether the Federal Circuit

has deemed that method-of-treatment claims are

categorically patent-eligible at Step One.

Even accepting the premise that the ’610 patent

is “directed to” a law of nature at Step One,

however, its claim elements are not routine and

conventional at Step Two.

Hikma seizes on

statements in Chief Judge Prost’s dissent to argue

that “[t]he audience of physicians treating

schizophrenia with iloperidone long predated the

31

’610 patent.” Pet. at 20 (quoting App. 48a (Prost,

C.J., dissenting)); see also Pet. at 18 (quoting App.

44a (Prost, C.J., dissenting)). As set forth above, the

record belies this. Iloperidone use was not routine

or conventional before the ’610 patent. It was

illegal; FDA had not yet approved iloperidone.

Hikma also contends that the administration

elements are “routine and conventional” because it

would be routine to perform studies to ascertain the

correct iloperidone dosages for specific patient

subpopulations. Pet. at 37. That answers the

wrong question.

Step Two asks whether the

additional elements of the patent claim are routine

and conventional, Mayo, 566 U.S. at 82; Alice, 573

at 221-22, not whether the inventors used routine

and conventional means to make their invention.

Moreover, it gets the answer wrong. Hikma’s expert

conceded at trial that clinical-trial design is not

routine or conventional, the district court found that

the ’610 inventors’ work was not obvious, and

Hikma chose not to appeal that finding. If their

work was non-obvious, it cannot have been “wellknown in the art,” which is the hallmark of the

routine-and-conventional inquiry at Step Two. See,

e.g., Mayo, 566 U.S. at 79.

III.

THE DECISION BELOW WILL NOT DELAY

ACCESS TO GENERIC DRUGS OR HARM

SOCIETY

The natural-law, abstract-idea, and naturalphenomena exceptions to patentability exist to

protect innovation: monopolization of those basic

tools of scientific research “might tend to impede

32

innovation more than it would tend to promote it.”

Mayo, 566 U.S. at 71. In Mayo, the American

Medical Association and other leading physician

groups as amici warned of the risks of monopolizing

“‘the body’s natural responses to illness and medical

treatment.’” Id. at 91 (quoting physician amicus

brief). Likewise, the challenge to the patents in

Myriad was brought by, among others, “medical

patients, advocacy groups, and . . . doctors.” 569

U.S. at 586.

Notably, Hikma has no amicus support from

doctors, from patients, or from innovators of any

kind.

Its support comes from academics,

professional lobbyists, and other generic-drug

companies.

Protecting their own interests, they warn that

the decision will incentivize innovators to list

patent-ineligible method-of-treatment patents in the

FDA “Orange Book” and improperly obtain 30month-stays of FDA approval for a generic drug.

But Congress explicitly contemplated that methodof-treatment patents would issue, and required

innovators to list those patents in the Orange Book.

And in the same Patent Act that includes Section

101, Congress provided that submitting an

Abbreviated New Drug Application for a generic

drug infringes not only patents on the drug itself,

but patents on “the use” of that drug. 35 U.S.C.

§ 271(e)(2)(A) (emphasis added); see Caraco Pharm.

Labs., Ltd. v. Novo Nordisk A/S, 566 U.S. 399, 405

(2012). New Drug Application owners must list in

the Orange Book “any patent which claims the drug

33

for which the applicant submitted the application or

which claims a method of using such a drug . . . .”

21 U.S.C. § 355(b)(1) (emphasis added).

The

biosimilars statute likewise contemplates litigation

See 35 U.S.C.

over method-of-use patents.

§ 271(e)(2)(C); 42 U.S.C. § 262(l)(3)(A).

Hikma’s and its amici’s position, on the other

hand, would radically rework the law of generic

drugs (a result that Inventia’s generic-drug-industry

brief eagerly embraces). If a method-of-treatment

patent is “directed to” a law of nature simply

because its therapeutic efficacy depends on

metabolic processes within the body (or, in

Inventia’s articulation, because “a patient’s body

determines if infringement occurs,” Inventia Br. at

16), then an enormous number of patents

specifically identified by the Patent Act will become

ineligible for patenting.

Whether iloperidone treats schizophrenia at all

depends on what happens in “a patient’s body,” yet

no one contends that using iloperidone to treat

schizophrenia would be unpatentable. Indeed, all

methods of treatment depend, at some level, on

what happens in a patient’s body.

Hikma

begrudgingly concedes that Section 101 would

permit a patent on the use of a known antiviral drug

to treat cancer, see Pet. at 21-22, but never explains

how that patent differs analytically from a patent on

treating some schizophrenia patients with

iloperidone at one dose and other patients at

another dose.

34

Petitioner’s amici go further, proposing a regime

under which essentially all method-of-treatment

patents would be ineligible. In their view, if an

inventor were to discover that the standard dose of

Tylenol effectively treats pancreatic cancer, the

courts would deem that insight to be in the prior art

and then ask only whether the dosage schedule was

routine and conventional. See Inventia Br. at 12-14,

19; Amicus Br. of Intellectual Property and

Innovation Professors, et al. at 7. There is no

support for that position in this Court’s cases, and it

is irreconcilable with Congress’s decision to make

method-of-use patents part of generic-drug and

biosimilar litigation.

IV.

THE PATENT OFFICE HAS NOT CREATED

A CATEGORICAL EXCEPTION FOR

METHODS-OF-TREATMENT TO THIS

COURT’S PRECEDENTS

Hikma suggests that the Patent Office reads the

Vanda decision as “ensur[ing] that all future

method-of-treatment patents will issue without

undergoing any real scrutiny” at Step One of the

Alice/Mayo analysis. Pet. at 29.

Hikma misreads the Patent Office guidance.

That is clear both from the June 2018 Memorandum

on which Hikma relies and from Subject Matter

Eligibility Guidance that the Patent Office issued

for public comment after Hikma filed its Petition.

The June 2018 Memorandum did not announce

that all method-of-treatment claims are patenteligible.

Had that been the Patent Office’s

35

conclusion, the Memorandum would have been one

sentence long. Instead, the Memorandum stressed

what this Court stressed in Alice and Mayo and the

Federal Circuit repeated in the decision below:

• In assessing patent eligibility, claims must be

evaluated “as a whole.” App. 97a.

• Method-of-treatment claims that “apply”

natural relationships, “as opposed to being ‘directed

to’ them,” are eligible for patenting. Id. at 98a

(emphasis in original).

• Whether the other claim elements are

“routine and conventional” is relevant at Step Two

of the Alice/Mayo analysis (which the Patent Office

calls Step 2B), but is not relevant if, at Step One (or,

in the Patent Office parlance, Step 2A), the claim is

not directed to a law of nature. Id.

From these principles, the June 2018

Memorandum concluded only what Mayo and Alice

already taught: method-of-treatment claims should

be considered patent-eligible at Step One of the

Alice/Mayo test where those claims “practically

apply,” without being directed to, “natural

relationships.” Id. at 98a-99a.

The June 2018 Memorandum ended with the

possibility of “further guidance in the area of subject

matter eligibility in the future.” Id. at 99a. The

Patent Office released that Guidance on January 7,

2019. The new Guidance, too, differentiates “claims

to principles in the abstract” and “claims that

integrate those principles into a practical

36

application.” 2019 Revised Patent Subject Matter

Eligibility Guidance, 84 Fed. Reg. 50, 51 (Jan. 7,

2019). It proposes that “A claim is not ‘directed to’ a

judicial exception, and thus is patent eligible, if the

claim as a whole integrates the recited judicial

exception into a practical application of that

exception.” Id. at 53. “A claim that integrates a

judicial exception into a practical application will

apply, rely on, or use the judicial exception in a

manner that imposes a meaningful limit on the

judicial exception, such that the claim is more than

a drafting effort designed to monopolize the judicial

exception.” Id. (emphases added).

The Guidance is completely consistent with the

law as this Court articulated it in Mayo and Alice.

And it treats the decision below as a fact-specific

application of this Court’s precedents, not as a

categorical exemption of method-of-treatment

claims from those precedents.

The Guidance

describes the decision below as “holding claims to

the practical application of the natural relationships

between iloperidone, CYP2D6 metabolism, and QTc

prolongation to treat schizophrenia, not merely the

recognition of those relationships, to be patent

eligible at Mayo/Alice step 1.” Id. at 55 n.26.

Finally, the new Guidance confirms why this

case is a poor vehicle for the Court to address

Section 101 further. The Guidance notes that the

law on Section 101 is “rapidly evolving,” id. at 51,

and it calls for public comment on the proposed

Guidance by March 8, 2019. The Guidance itself

37

may evolve or change in response to public

commentary. Id. at 57.

38

CONCLUSION

For the foregoing reasons, Hikma’s Petition

should be denied.

Respectfully submitted,

Nicholas Groombridge

Counsel of Record

Eric Alan Stone

Kira Alexis Davis

Josephine Young

Daniel J. Klein

PAUL, WEISS, RIFKIND,

WHARTON & GARRISON LLP

1285 Avenue of the Americas

New York, NY 10019

(212) 373-3212

ngroombridge@paulweiss.com

Counsel for Respondent

FEBRUARY 12, 2019