Amicus Curiae 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 A ppeals for the Federal Circuit

BRIEF FOR THE ASSOCIATION FOR

ACCESSIBLE MEDICINES AND CERTAIN

INDIVIDUAL COMPANIES AS AMICI

CURIAE IN SUPPORT OF THE PETITION

Douglass C. Hochstetler

Counsel of Record

Sarita M. Matheson

Kelley Drye & Warren LLP

333 West Wacker Drive, Suite 2600

Chicago, IL 60606

(312) 857-7070

dhochstetler@kelleydrye.com

Counsel for Amici Curiae

285979

A

(800) 274-3321 • (800) 359-6859

i

TABLE OF CONTENTS

Page

TABLE OF CONTENTS . . . . . . . . . . . . . . . . . . . . . . . . . . i

TABLE OF APPENDICES . . . . . . . . . . . . . . . . . . . . . . iii

TABLE OF CITED AUTHORITIES . . . . . . . . . . . . . . . iv

INTERESTS OF AMICI CURIAE . . . . . . . . . . . . . . . . 1

SUMMARY OF THE ARGUMENT . . . . . . . . . . . . . . . 2

ARGUMENT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

I.

The Conflict Between Mayo and the Decision

Below Warrants Resolution by this Court . . . . . 4

A. The Decision Below Undermines

Comp et it ion by T hw a r t i ng t he

Congressional Purpose of the HatchWaxman Act . . . . . . . . . . . . . . . . . . . . . . . . . . 4

B. Several Federal Circuit Judges Have

Expressed the Need for Clarification

of Mayo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

II. The Decision Below A llows the PTO

to Re-Adopt the Approach to Section

101 that this Court Rejected in Mayo . . . . . . . . . 8

III. F o r S e c t i o n 1 0 1 P u r p o s e s , t h e

Method of T reatment Cla i ms Here

ii

Table of Contents

Page

and the Claims Unanimously Struck

Down in Mayo are the Same . . . . . . . . . . . . . . . 12

A. As in Mayo, the Claims Here Seek to

Monopolize a Law of Nature by Reciting

Conventional Activity . . . . . . . . . . . . . . . . . 12

B. In Both Mayo and the Decision Below,

a Law of Nature Determined Whether

the Claim is Infringed . . . . . . . . . . . . . . . . 15

CONCLUSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

iii

TABLE OF APPENDICES

Page

APPENDIX A — 2019 REVISED PATENT

SUBJECT MATTER ELIBILITY GUIDANCE

FOR THE UNITED STATES PATENT AND

TRADEMARK OFFICE . . . . . . . . . . . . . . . . . . . . . . 1a

APPENDIXB—UNITED STATES PATENT AND

TRADEMARK OFFICE AMENDMENT

TO NON-FINAL REJECTION . . . . . . . . . . . . 6a

iv

TABLE OF CITED AUTHORITIES

Page

CASES

Ariosa Diagnostics, Inc. v. Sequenom, Inc.,

809 F.3d 1282 (Fed. Cir. 2015) (Dyk, J.,

concurring in denial of rehearing en banc) . . . . . . 6, 7

Berkheimer v. HP Inc.,

890 F.3d 1369 (Fed. Cir. 2018) (Lourie, J.,

joined by Newman, J., concurring in

denial of rehearing en banc) . . . . . . . . . . . . . . . . . . . . 7

Caraco Pharm. Labs., Ltd. v. Novo Nordisk A/S,

566 U.S. 399 (2012) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Eli Lilly & Co. v. Medtronic, Inc.,

496 U.S. 661 (1990) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

F.T.C. v. Actavis, Inc.,

570 U.S. 136 (2013) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Funk Bros. Seed Co. v. Kalo Inoculant Co.,

333 U.S. 127 (1948) . . . . . . . . . . . . . . . . . . . . . . 9, 10, 15

Le Roy v. Tatham,

55 U.S. (14 How.) 156 (1853) . . . . . . . . . . . . . . . . . . . . 15

Mayo Collaborative Servs. v.

Prometheus Labs, Inc.,

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

v

Cited Authorities

Page

Parker v. Flook,

437 U.S. 584 (1978) . . . . . . . . . . . . . . . . . . . . . . . . . 2, 13

STATUTES

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

Drug Price Competition and Patent Term Restoration

Act of 1984, Pub. L. No. 98-417, 98 Stat. 1585 . . . . . . 4

Other Authorities

2019 Revised Patent Subject Matter Eligibility

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

(App. 1a-5a) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3, 4, 9

Brief for the United States as Amicus Curiae

Supporting Neither Party, Mayo Collaborative

Servs. v. Prometheus Labs., Inc., 566 U.S.

66 (2012) (No. 10-1150), 2011 WL 4040414 . . . . . 10, 11

Robert H. Bahr, Memo, Recent Subject Matter

El i g i b i li t y D e c i s i o n : Va n d a Ph a r m .

Inc. v. West-Ward Pharm. (June 7, 2018)

(Pet. App. 95a-99a) . . . . . . . . . . . . . . . . . . . . . . . 6, 9, 14

Curt D. Wolfgang, et al., United States Patent

and Trademark Office Amendment to NonFinal Rejection, Method for Administration

of I loper idone, Appl ic at ion 11 /576 ,178

(March 20, 2013) (App. 6a-8a) . . . . . . . . . . . . . . . . . . 15

vi

Cited Authorities

Page

Quinn, Judge Stoll tells AIPLA Alice/Mayo ‘a difficult

line of cases to administer’ IPWatchdog (Oct. 26,

2018) http://www.ipwatchdog.com/2018/10/26/

judge-stoll-aipla-alice-mayo/id=102708/ . . . . . . . . . . 7

1

INTERESTS OF AMICI CURIAE1

Amicus Curiae, the Association for Accessible

Medicines (“AAM”), is a nonprofit, voluntary association

representing the interests of the generic and biosimilar

medicines industry. AAM represents manufacturers

and distributors of finished generic and biosimilar

pharmaceuticals, manufacturers and distributors of

bulk active pharmaceutical ingredients, and suppliers of

other goods and services to the generic and biosimilar

pharmaceutical industry. Its members provide Americans

with generic and biosimilar medicines that are as safe and

effective as their brand-name counterparts, but that are

substantially more affordable.

AAM seeks to provide courts with the perspective

of the generic and biosimilar pharmaceutical industry

on important legal issues impacting its members, and

to highlight the potential industry-wide consequences of

significant pending cases.

A A M ’s members a re f requent ly i nvolved i n

pharmaceutical litigation in which they rely on invalidity

defenses such as Section 101 patent eligibility. Invalid

patents undermine the legitimacy of the patent system,

stifle competition, and impede access to low-cost medicines.

Accordingly, AAM members have significant interest in

1. Pursuant to Rule 37.6, amici state that no counsel for any

party authored this brief in whole or in part, and no person other

than amici or its counsel have made any monetary contribution

intended to fund the preparation or submission of this brief. All

parties to this case received timely notice under Rule 37.2(a) of

amici’s intent to file this brief, and all parties consented to the

filing of this brief.

2

ensuring that brand companies enforce drug monopolies

only on patent-eligible claims.

Amici Cur ia e , Inventia Hea lthca re Li m it ed

(“Inventia”) and Mylan Pharmaceuticals, Inc., (“Mylan”)

have a direct interest in the present petition because

of a current lawsuit in the District of Delaware, which

involves the same patent-at-issue—U.S. Patent 8,586,610

(“the ’610 patent”). See Vanda Pharms. Inc., v. Inventia

Healthcare Ltd., C.A. No. 15-362 (D. Del.). Inventia, the

named defendant, is the manufacturer of the drug in

question, iloperidone, and Mylan has contracted with

Inventia to market the drug. The lawsuit is stayed pending

the outcome of Hikma’s petition for writ of certiorari.

Because subject matter eligibility is a threshold inquiry,

this Court’s decision on the patent eligibility of the ’610

patent will undoubtedly have direct implications on the

case below. See Parker v. Flook, 437 U.S. 584, 593 (1978)

(“The obligation to determine what type of discovery is

sought to be patented must precede the determination of

whether that discovery is, in fact, new or obvious.”).

SUMMARY OF THE ARGUMENT

Hikma’s petition for certiorari addresses a matter

of national importance warranting review. The Court’s

unanimous decision in Mayo Collaborative Servs. v.

Prometheus Labs, Inc., 566 U.S. 66 (2012) set forth the

requirements for patent eligibility under 35 U.S.C § 101 of

the Patent Act and invalidated a claimed method because

it directed the audience to apply a natural law in a routine

way. The decision below has been widely understood to

carve out a whole category of method of treatment patents

and declared them not subject to those requirements. The

3

question presented is thus whether patents that claim

a method of medically treating a patient automatically

satisfy Section 101, even if they apply a natural law

using routine and conventional steps. Amici respectfully

argue that the decision below directly conflicts with

Mayo and warrants review due to the large number of

pharmaceuticals and other products affected by the ruling.

Denial of the petition would lead to untold numbers

of future patents improperly issued and existing patents

improperly enforced. The Patent and Trademark Office

(PTO) has embraced the Federal Circuit’s divided opinion

below as giving it license to adopt a position that this

Court rejected in Mayo. As explained in this brief, there

is no difference, for purposes of Section 101, between the

method of treatment claims upheld in the decision below

and the claims struck down by this Court in Mayo. The

claims in both cases combined a natural law with the

same two method steps previously used by those in the

field. And the result in both cases was an unpatentable

claim directed to a law of nature because a patient’s body

determined if infringement occurred.

The widely felt urgency for this Court to clarify the

implications of Mayo for existing as well as future patents

was acknowledged earlier this month by the PTO: “[m]any

stakeholders, judges, inventors, and practitioners across

the spectrum have argued that something needs to be

done to increase clarity and consistency in how Section

101 is currently applied.” See 2019 Revised Patent Subject

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

(emphasis added) (“2019 PTO Guidance”) (App. 2a).

4

We respectfully submit that what “needs to be done

to increase clarity and consistency in how Section 101 is

currently applied” is to grant Hikma’s petition. Id. If the

categorical exception to Mayo stands, Section 101 eligibility

for future patents will depend on the draftsman’s art of

camouflaging patent-ineligible claims as treatment steps.

Allowing such a practice will also have the immediate

consequence of improperly extending the monopoly period

of brand name drugs, and wrongly depriving the public

of the generic version of a medicine—eleven more years

in the case of iloperidone—thus forcing taxpayers and

patients to pay monopoly prices of pharmaceuticals for

far longer than the patent system should allow under this

Court’s holding in Mayo.

This case illustrates the real world implications when

confusion about patent eligibility reigns. This Court can

and should dispel the confusion. Hikma’s petition for

certiorari should be granted.

ARGUMENT

I.

The Conflict Between Mayo and the Decision Below

Warrants Resolution by this Court

A.

The Decision Below Undermines Competition

by Thwarting the Congressional Purpose of

the Hatch-Waxman Act

The purpose of the Drug Price Competition and

Patent Term Restoration Act of 1984,2 commonly known as

the Hatch-Waxman Act, was to “speed[ ] the introduction

of low-cost generic drugs to market thereby furthering

2. Pub. L. No. 98-417, 98 Stat. 1585.

5

drug competition.” See e.g., F.T.C. v. Actavis, Inc., 570 U.S.

136, 142 (2013) (internal citation omitted). 3 Thwarting that

statutory purpose, brand companies continue to abuse

the patent system to enforce monopolies on brand drugs

in a practice known as “evergreening”—filing patents

on methods of using the same drug and thereby delaying

generic access.4

This is a textbook case. Vanda’s patent on the

iloperidone compound—U.S. Reissue Patent 39,198—

expired on November 15, 2016. Petition Appendix (“Pet.

App.”) 2a. The Federal Circuit’s conclusion that Mayo does

not apply to the ’610 patent because it claims a method

of treatment allows Vanda to thwart the Congressional

purpose for almost eleven more years (until November

2, 2027).

Method of treatment patent claims, like the ’610

patent, are common fare for pharmaceutical patents.

Underscoring the high frequency of these patents is the

3. See also Caraco Pharm. Labs., Ltd. v. Novo Nordisk A/S,

566 U.S. 399, 405 (2012); Eli Lilly & Co. v. Medtronic, Inc., 496

U.S. 661, 676 (1990).

4. See Caraco Pharm. Labs at 405:

Because the FDA cannot authorize a generic drug

that would infringe a patent, the timing of an ANDA’s

approval depends on the scope and duration of the

patents covering the brand-name drug. Those patents

come in different varieties. One type protects the

drug compound itself. Another kind—the one at issue

here—gives the brand manufacturer exclusive rights

over a particular method of using the drug. In some

circumstances, a brand manufacturer may hold such

a method-of-use patent even after its patent on the

drug compound has expired.

6

fact that 2,379 unique method patents are listed in the

Orange Book. See Petition at 26-27. Each listed method

patent can enable a brand name drug manufacturer to

obtain a 30-month automatic stay of generic competition

when in litigation. Yet, as this brief later explains, there is

no practical distinction for Section 101 purposes between

the claims addressed in Mayo and the method of treatment

claims presented here. These patents serve to take away

generic drug treatments that, under Mayo, rightfully

belong to the public.

If this Court remains silent, the PTO can be expected

to issue, and the lower courts enforce, an untold number of

improper patents because they are denominated “method

of treatment” patents. And indeed, the PTO has already

issued guidance to examiners based on this case asserting

that “method of treatment claims (which apply natural

relationships as opposed to being ‘directed to’ them) were

identified by the Supreme Court as not being implicated

by its decisions in Mayo and Myriad . . . .” See Robert H.

Bahr, Memo, Recent Subject Matter Eligibility Decision:

Vanda Pharm. Inc. v. West-Ward Pharm. (June 7, 2018)

(emphasis is that of the PTO) (Pet. App. 98a) (“2018 PTO

Memo”). Such a broad categorical exemption from Section

101 for method of treatment patents urgently warrants

review.

B. Several Federal Circuit Judges Have Expressed

the Need for Clarification of Mayo

On the issue of Section 101, Federal Circuit judges

have repeatedly requested guidance from this Court.

Judge Dyk wrote in Ariosa, “further illumination as

to the scope of Mayo would be beneficial . . . and any

7

further guidance must come from the Supreme Court, not

this court.” See Ariosa Diagnostics, Inc. v. Sequenom,

Inc., 809 F.3d 1282, 1287 (Fed. Cir. 2015) (concurring in

denial of rehearing en banc). Judge Stoll recently stated

at an American Intellectual Property Law Association

meeting, “‘one of the more challenging issues I’ve seen

since I’ve been at the court is the 101 test and the Alice/

Mayo test. . . to the extent there is any need for change

that would be for Congress or the Supreme Court.’” See

Quinn, Judge Stoll tells AIPLA Alice/Mayo ‘a difficult

line of cases to administer’, IPWatchdog (Oct. 26, 2018)5;

see also Berkheimer v. HP Inc., 890 F.3d 1369, 1375 (Fed.

Cir. 2018) (Lourie, J., joined by Newman, J., concurring in

denial of rehearing en banc) (“Section 101 issues certainly

require attention beyond the power of this court.”).

The author of the decision below has been critical of

Mayo.6 The decision below circumvents Mayo by seizing

upon isolated statements in the Mayo opinion to support

5. http://www.ipwatchdog.com/2018/10/26/judge-stoll-aiplaalice-mayo/id=102708/.

6. See Berkheimer at 1375 (Fed. Cir. 2018) (Lourie, J., joined

by Newman, J., concurring in denial of rehearing en banc):

The Supreme Court whittled away at the § 101

statute in Mayo by analyzing abstract ideas and

natural phenomena with a two-step test, including

looking for an “inventive concept” at step two,

thereby bringing aspects of §§ 102 and 103 into

the eligibility analysis….We now are interpreting

what began, when it rarely arose, as a simple § 101

analysis, as a complicated multiple-step consideration

of inventiveness (“something more”), with the result

that an increasing amount of inventive research is no

longer subject to patent.

8

its conclusion that Vanda’s method of treatment claims

are not directed to a natural law. See Petition at 19-22.

The dissenting judge saw clearly that the net effect of the

opinion was a decision contrary to the holding in Mayo:

“[w]hatever weight can be ascribed to the foregoing

statements about methods of treatment, we remain

beholden to the holding of Mayo, which, in my view,

requires us to find the claims directed to a natural law at

step one.” Pet. App. 49a; see also Petition at 19-22.7

II. The Decision Below Allows the PTO to Re-Adopt the

Approach to Section 101 that this Court Rejected

in Mayo

Underscoring the national importance of this decision,

the PTO issued two new guidances on Section 101 after

the Federal Circuit issued its opinion. In these guidances,

7. See also Pet. App. 47a-48a, (Prost., C. J., dissenting)

(internal citations omitted):

The Court in Mayo found that the claim limitation

concerning “administering” a thiopurine drug to a

patient “simply refer[red] to the relevant audience,

namely doctors who treat patients with certain

diseases with thiopurine drugs”—an audience that

existed long before the patent disclosure. So too here.

The audience of physicians treating schizophrenia

with iloperidone long predated the ’610 patent. The

patent simply discloses the natural law that a known

side effect of the existing treatment could be reduced

by administering a lower dose to CYP2D6 poormetabolizers. It claims no more than instructions

directing that audience to apply the natural law in a

routine and conventional manner. The majority fails

to reconcile this substantive similarity between our

case and Mayo.

9

which specifically discuss this case, the PTO interpreted

the divided decision below to effectively carve out method

of treatment claims from Section 101: “[t]he Mayo claims

were not ‘method of treatment’ claims that practically

apply a natural relationship.” 2018 PTO Memo (Pet. App.

98a). After Hikma submitted the petition for certiorari,

the PTO reaffirmed, in the 2019 PTO Guidance, its

understanding of the decision below, which established a

framework that goes beyond method of treatment claims:

“[o]nly when a claim recites a judicial exception and fails to

integrate the exception into a practical application, is the

claim ‘directed to’ a judicial exception, thereby triggering

the need for further analysis pursuant to the second step

of the Alice/Mayo test ….” App. 4a. 8

Fairly read, however, this Court’s precedent does not

stand for the proposition that claims which are a “practical

application” of a natural relationship necessarily satisfy

Section 101, particularly where the steps are routine and

conventional. Instead, this Court’s pre-Mayo precedent

held exactly the opposite. See Funk Bros. Seed Co. v. Kalo

Inoculant Co., 333 U. S. 127, 131 (1948) (holding a practical

application of a law of nature invalid under Section 101)

(“The aggregation of select strains of the several species

8. In the 2019 PTO Guidance, the PTO explicitly characterized

the decision below as a “practical application.” See App. 5a:

See also Vanda Pharm. Inc. v. West-Ward Pharm. Int’l

Ltd., 887 F.3d 1117, 1135 (Fed. Cir. 2018) (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 (USPTO Step 2A)), and USPTO

Vanda Memorandum (discussing Vanda).

10

into one product is an application of that newly-discovered

natural principle. But however ingenious the discovery of

that natural principle may have been, the application of

it is hardly more than an advance in the packaging of the

inoculants.”).

As the unanimous nature of the Mayo opinion suggests,

Mayo is not an aberration in this Court’s jurisprudence.

Rather Mayo is wholly consistent with Funk. Both cases

instruct that merely combining conventional activity with

a newly discovered natural law is not patent eligible under

Section 101.

In its amicus brief to this Court in Mayo, the

Government made the argument, with the PTO as a

signatory, that the administering and determining

steps recited in the Mayo claims constituted a practical

application of a law of nature that made the claimed

invention patent eligible. See Brief for the United States

as Amicus Curiae (“Those steps describe a patent-eligible

process under Section 101. The claim recites a series

of acts in the physical world that achieve a useful end

(treatment of auto-immune disorders) by transforming

the body chemistry of the patient.”).9

9. Brief for the United States as Amicus Curiae Supporting

Neither Party at pg. 14, Mayo Collaborative Servs. v. Prometheus

Labs., Inc., 566 U.S. 66 (2012) (No. 10-1150), 2011 WL 4040414.

The complete quote is as follows:

Cla i m 1 of the ’6 2 3 pat ent recit es a method

comprising two affirmative steps: (1) “administering

a drug providing 6-thioguanine to a subject,” and

(2) “determining the level of 6-thioguanine in said

subject.” Those steps describe a patent-eligible

11

Importantly, that argument—which so closely

parallels the PTO’s new guidance—was unanimously

rejected in Mayo:

The Government argues that virtually any

step beyond a statement of a law of nature

itself should transform an unpatentable law of

nature into a potentially patentable application

sufficient to satisfy § 101’s demands . . . This

approach, however, would make the “law of

nature” exception to § 101 patentability a dead

letter. The approach is therefore not consistent

with prior law.

Mayo, 566 U. S. at 89.10

Also importantly, the claim at issue in this case, and

the claim in Mayo, recited the same method steps: a

determining step and an administering step. The steps

process under Section 101. The claim recites a series

of acts in the physical world that achieve a useful end

(treatment of auto-immune disorders) by transforming

the body chemistry of the patient.

10. Mayo, 566 U.S. at 89, omitted portion of the quote is as

follows:

The Government does not necessarily believe that

claims that (like the claims before us) extend just

minimally beyond a law of nature should receive

patents. But in its view, other statutory provisions—

those that insist that a claimed process be novel, 35

U.S.C. § 102, that it not be “obvious in light of prior

art,” § 103, and that it be “full[y], clear[ly], concise[ly],

and exact[ly]” described, § 112—can perform this

screening function. In particular, it argues that these

claims likely fail for lack of novelty under § 102.

12

in the claims are reversed (in this case, determining

comes before administering, while in Mayo the order is

reversed), but in both claims the natural law is applied by

the same two steps. See Petition at 34-35.

With this background, the method of treatment claims

here are revealed to be analytically indistinguishable

from the claims in Mayo. Inasmuch as a claim reciting

the steps of administering a drug and determining the

metabolic result is (per Mayo) directed to a law of nature,

so too is a claim that recites the steps of first determining

the metabolism and then administering the drug. There

is no reasoned basis for finding that one is directed to a

natural law and the other not.

The decision below has thus led to the incongruous

categorical rule that a “practical application” of a natural

law satisfies Section 101 regardless of whether the steps

are routine and conventional. Without review from this

Court, this broad exemption from Mayo for “practical

applications” of a natural law can be expected to produce

a flood of improperly issued and enforced patents—all the

while keeping the public from generic versions of these

drugs.

III. For Section 101 Purposes, the Method of Treatment

Claims Here and the Claims Unanimously Struck

Down in Mayo are the Same

A.

As in Mayo, the Claims Here Seek to Monopolize

a Law of Nature by Reciting Conventional

Activity

The similarities between the patent at issue here

and the patent at issue in Mayo help remove the shroud

13

of skillful patent drafting from an attempt to monopolize

the operation of a law of nature. As Mayo noted, this

Court’s precedent “warn[s] us against interpreting patent

statutes in ways that make patent eligibility ‘depend

simply on the draftsman’s art’ without reference to the

‘principles underlying the prohibition against patents for

[natural laws].’” Mayo, 566 U.S. at 72 (citing Parker v.

Flook, 437 U.S. 584, 593 (1978)). One of those principles

is that inventiveness must be examined apart from the

law of nature. See Flook, 437 U.S. at 594 (“Even though

a phenomenon of nature or mathematical formula may

be well known, an inventive application of the principle

may be patented. Conversely, the discovery of such a

phenomenon cannot support a patent unless there is some

other inventive concept in its application.”) (emphasis

added).

The putative invention of the Vanda patent concerns

adjusting the dose of the antipsychotic drug, iloperidone,

based on a patient’s naturally occurring genetic makeup. 11

For a method of treatment using iloperidone to be patent

eligible, the method steps must, according to Flook, add

some inventive concept separate and apart from the

natural law. Here there is no such inventive concept for

11. See C.A. App. 38, the ’610 patent, col. 1, ll. 53-61:

Mutations in the CYP2D6 gene have been associated

with a number of drug metabolism-related phenotypes.

These include the ultra rapid metabolizer (UM),

extensive metabolizer (EM), intermediate metabolizer

(IM), and poor metabolizer (PM) phenoty pes.

Where a particular drug is capable of producing

unwanted physiological effects in its metabolized or

non-metabolized forms, it is desirable to determine

whether a patient is a poor metabolizer of the drug

prior to its administration.

14

at least two reasons. First, it is the same pair of method

steps (determining and administering) involved here

as in Mayo, and this Court concluded in Mayo that “the

steps add nothing of significance to the natural laws

themselves.”12 Id. at 87. Second, as discussed below, the

patentee here admitted these steps were conventional

activity.

Genotype testing, and the specific dosages recited in

the claims of the ’610 patent, were conventional activity

previously engaged in by those in the field. See Pet.

App. 47a (C. J. Prost, dissenting) (concluding both the

genotyping and specific dosages add nothing inventive).

See also 2018 PTO Memo, Pet. App. 97a, where the PTO

referred to “the arguably conventional genotyping and

treatment steps.” In fact, the body of the ’610 patent

describes that its genotyping testing merely employed

commercially available kits used according to the

manufacturer’s instructions.13 C.A. App. 40. Similarly,

12. Mayo, 566 U.S. at 87:

We need not, and do not, now decide whether were the

steps at issue here less conventional, these features of

the claims would prove sufficient to invalidate them.

For here, as we have said, the steps add nothing of

significance to the natural laws themselves. Unlike,

say, a typical patent on a new drug or a new way of

using an existing drug, the patent claims do not confine

their reach to particular applications of those laws.

13. See C.A. App. 40, the ’610 Patent, col. 5-6, ll. 56-3:

Amplification was performed on 40-100 ng of genomic

DNA using a GC-rich PCR kit (Roche Diagnostics,

Mannheim, Germany) according to the manufacturer’s

recommendations.

15

during prosecution of the ’610 patent at the PTO, Vanda

admitted that a key prior art reference, Jain, described

the claimed dosages.14

B. In Both Mayo and the Decision Below, a Law

of Nature Determined Whether the Claim is

Infringed

This Court has long instructed that Section 101

protects against efforts to monopolize the operation of a

law of nature, because a natural law belongs to all. See

e.g., Funk at 130 (1948) citing Le Roy v. Tatham, 55 U.S.

(14 How.) 156 (1853).15 This case involves such an attempt

***

Third Wave Technologies, Inc (Madison, Wis.)

developed the probe sets for genotyping. Genotyping

was performed on PCR products using the Invader®

assay (Lyamichev 1999) (Third Wave Technologies, Inc)

according to the manufacturer’s recommendations.

14. See Curt D. Wolfgang, et. al, United States Patent and

Trademark Office Amendment to Non-Final Rejection, Method

for Administration of Iloperidone, Application 11/576,178 (March

20, 2013) (App. 6a-8a), where the patentee, Vanda, quoted without

disagreement the PTO’s characterization of Jain (App. 7a):

Jain provides an overview of several studies of

iloperidone, teaching that daily dosages of iloperidone

up to 24 mg/day have been ‘found to be well tolerated’….

Jain also discloses a long term study of dosages of 4

-16 mg/day (citation omitted), as well as the finding of

efficacy at dosages of 8 mg/day….

15. Funk at 130 (1948) (internal citation omitted):

The qualities of these bacteria, like the heat of the

sun, electricity, or the qualities of metals, are part

16

to monopolize a law of nature that is at least as blatant as

Mayo. Accordingly, if the decision below is not reviewed,

Mayo itself is undermined.

In Mayo, infringement depended upon how the patient’s

body metabolized a given dose of a drug. If the drug

dosage produced a level of the metabolite (6-thioguanine)

less than 230 pmol, or more than 400 pmol, then the doctor

infringed. However, if the 6-thioguanine level was between

230 and 400 pmol, there was no infringement. The same

action by the doctor thus infringed, or did not infringe,

depending upon how the body metabolized the drug.16

of the storehouse of knowledge of all men. They are

manifestations of laws of nature, free to all men and

reserved exclusively to none. He who discovers a

hitherto unknown phenomenon of nature has no claim

to a monopoly of it which the law recognizes.

16. Mayo representative claim 1 (Pet. App. 44a-45a):

A method of optimizing therapeutic efficacy for

treatment of an immune-mediated gastrointestinal

disorder, comprising:

(a) administering a drug providing 6–thioguanine to a

subject having said immune-mediated gastrointestinal

disorder; and

(b) determining the level of 6–thioguanine in said

subject having said immune-mediated gastrointestinal

disorder,

wherein the level of 6–thioguanine less than about

230 pmol per 8x10 8 red blood cells indicates a need

to increase the amount of said drug subsequently

administered to said subject and

17

The representative claim at issue in the present case

has a similar defect. The district court found one instance

of infringement, citing the trial testimony of plaintiff’s

expert Dr. Gus Alva about his Patient No. 1.17 Here is

the pertinent excerpt of the trial testimony cited by the

district court:

Q. This patient had a genotyping test in 2013

and was an extensive metabolizer. Correct?

A. Correct.

Q. And then we had one treatment in 2013 that

was 12 milligrams per day. Correct?

A. Yes.

Q. And two treatments in 2014 that were 12

milligrams per day. Correct?

A. Yes.

Q. And two treatments in 2015 that were 12

milligrams per day. Correct?

A. Yes.

wherein the level of 6–thioguanine greater than about

400 pmol per 8x10 8 red blood cells indicates a need

to decrease the amount of said drug subsequently

administered to said subject.

17. Pet. App. 86a.

18

Q. And then one treatment in 2015 that was

16 milligrams a day and one that was 20

milligrams per day. Correct?

A. Correct.

C.A. App. 6999.

Dr. A lva would have been infringing the ’610

patent from 2013-2015 if Patient 1 had been a CYP2D6

poor metabolizer, because giving 12 mg/day to a poor

metabolizer is an infringement.18 The administration of

18. See Claim 1 of the ’610 patent (Pet. App. 46a) (emphasis

added):

A method for treating a patient with iloperidone,

wherein the patient is suffering from schizophrenia,

the method comprising the steps of:

determining whether the patient is a CYP2D6 poor

metabolizer by:

obtaining or having obtained a biological sample from

the patient;

and

performing or having performed a genotyping assay

on the biological sample to determine if the patient has

a CYP2D6 poor metabolizer genotype; and

if the patient has a CYP2D6 poor metabolizer

genotype, then internally administering iloperidone

to the patient in an amount of 12 mg/day or less, and

if the patient does not have a CYP2D6 poor metabolizer

genotype, then internally administering iloperidone

to the patient in an amount that is greater than 12

mg/day, up to 24 mg/day,

19

12 mg/day for those two years was not an infringement,

however, because Patient No. 1’s genetic makeup was not

that of a poor metabolizer.

Similarly, Dr. Alva became an infringer in 2015 when

he increased the dosage to 16 mg/day. The administration

of 16 mg/day became an act of infringement because

Patient No. 1 “does not have a CYP2D6 poor metabolizer

genotype” (quoting claim 1 of the ’610 patent). Thus, as in

Mayo, how the patient metabolized the drug determined

whether the drug was being used in an infringing manner.

As noted in the prior section, there is no genuine

dispute that the iloperidone doses used by Dr. Alva—the

“non-infringing” 12 mg dose and the “infringing” 16 mg

dose—were both in the prior art. When this conventional

activity is removed from the claim, all that remains is a

naked attempt to monopolize the operation of a law of

nature. This is because whether conventional activity

infringes, or does not infringe, depends upon how the

body metabolizes iloperidone.

Just as in Mayo, such a claim is directed to a natural

law because a patient’s body determines if infringement

occurs. The claim here does not recite “a new way of using

an existing drug,” Mayo at 87 (emphasis added). Rather

it recites an old way of using an existing drug that may

have benefits depending upon the workings of a newlywherein 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 than it would be if the iloperidone were

administered in an amount of greater than 12 mg/

day, up to 24 mg/day.

20

discovered natural principle. Unless Mayo is to be honored

only in the breach rather than in the observance, review

should be granted of the decision below.

CONCLUSION

The decision below has created confusion in the law

that threatens harm to the public. In concluding that

Vanda’s method of treatment claims are not directed to

a law of nature, the majority opinion opened the door for

a rule which effectively exempts a “practical application”

of a natural law from Section 101. This Court’s precedent,

however, is contrary to such a rule. Allowing the decision

below to stand will improperly extend the monopoly period

of brand name drugs, and wrongly deprive the public of

generic medicines.

Before the decision below does more damage, both

to the coherency of the law and to the public interest

in affordable medicines, Hikma’s petition for certiorari

should be granted.

Respectfully submitted,

Douglass C. Hochstetler

Counsel of Record

Sarita M. Matheson

Kelley Drye & Warren LLP

333 West Wacker Drive, Suite 2600

Chicago, IL 60606

(312) 857-7070

dhochstetler@kelleydrye.com

January 28, 2019

Counsel for Amici Curiae

APPENDIX

1a

A PaTENT SUBjECT

APPENDIx A — 2019Appendix

REVISED

MaTTER ELIBILITY GUIDaNCE FOR THE

UNITED STaTES PaTENT aND

TRaDEMaRk OFFICE

DEPARTMENT OF COMMERCE

UnIted States Patent

and TrademarK OffIce

Docket No. PTO-P-2018-0053

2019 REVISED PaTENT SUBjECT MaTTER

ELIGIBILITY GUIDaNCE

***

Patent subject matter eligibility under 35 U.S.C. 101

has been the subject of much attention over the past decade.

Recently, much of that attention has focused on how to

apply the U.S. Supreme Court’s framework for evaluating

eligibility (often called the Alice/Mayo test).1 Properly

applying the Alice/Mayo test in a consistent manner has

proven to be difficult, and has caused uncertainty in this

area of the law. Among other things, it has become difficult

in some cases for inventors, businesses, and other patent

stakeholders to reliably and predictably determine what

subject matter is patent-eligible. The legal uncertainty

surrounding Section 101 poses unique challenges for the

USPTO, which must ensure that its more than 8500 patent

1. Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 573 U.S. 208, 217-18

(2014) (citing Mayo Collaborative Servs. v. Prometheus Labs., Inc.,

566 U.S. 66 (2012)).

2a

Appendix A

examiners and administrative patent judges apply the

Alice/Mayo test in a manner that produces reasonably

consistent and predictable results across applications, art

units and technology fields.

Since the Alice/Mayo test was announced and

began to be extensively applied, the courts and the

USPTO have tried to consistently distinguish between

patent-eligible subject matter and subject matter falling

within a judicial exception. Even so, patent stakeholders

have expressed a need for more clarity and predictability

in its application. In particular, stakeholders have

expressed concern with the proper scope and application

of the “abstract idea” exception. Some courts share these

concerns, for example as demonstrated by several recent

concurrences and dissents in the U.S. Court of Appeals

for the Federal Circuit (“Federal Circuit”) calling for

changes in the application of Section 101 jurisprudence. 2

Many stakeholders, judges, inventors, and practitioners

across the spectrum have argued that something needs to

be done to increase clarity and consistency in how Section

101 is currently applied.

To address these and other concerns, the USPTO is

revising its examination procedure with respect to the

2. See, e.g., Interval Licensing LLC v. AOL, Inc., 896 F.3d 1335,

1348 (Fed. Cir. 2018) (Plager, J., concurring in part and dissenting

in part); Smart Sys. Innovations, LLC v. Chicago Transit Auth.,

873 F.3d 1364, 1377 (Fed. Cir. 2017) (Linn, J., dissenting in part and

concurring in part); Berkheimer v. HP Inc., 890 F.3d 1369, 1376 (Fed.

Cir. 2018) (Lourie, J., joined by Newman, J., concurring in denial of

rehearing en banc).

3a

Appendix A

first step of the Alice/Mayo test 3 (Step 2A of the USPTO’s

Subject Matter Eligibility Guidance as incorporated into

the Manual of Patent Examining Procedure (“MPEP”)

2106)4 by: (1) Providing groupings of subject matter that

is considered an abstract idea; and (2) clarifying that a

claim is not “directed to” a judicial exception if the judicial

exception is integrated into a practical application of that

exception.

Section I of this 2019 Revised Patent Subject Matter

Eligibility Guidance explains that the judicial exceptions

are for subject matter that has been identified as the

“basic tools of scientific and technological work,”5 which

includes “abstract ideas” such as mathematical concepts,

certain methods of organizing human activity, and

mental processes; as well as laws of nature and natural

phenomena. Only when a claim recites a judicial exception

does the claim require further analysis in order to

determine its eligibility. The groupings of abstract ideas

contained in this guidance enable USPTO personnel to

3. The first step of the Alice/Mayo test is to determine whether

the claims are “directed to” a judicial exception. Alice, 573 U.S. at

217 (citing Mayo, 566 U.S. at 77).

4. All references to the MPEP in the 2019 Revised Patent

Subject Matter Eligibility Guidance are to the Ninth Edition,

Revision 08-2017 (rev. Jan. 2018), unless otherwise indicated.

5. Mayo, 566 U.S. at 71 (“Phenomena of nature, though just

discovered. mental processes, and abstract intellectual concepts

are not patentable, as they are the basic tools of scientific and

technological work” (quoting Gottschalk v. Benson, 409 U.S. 63, 67

(1972)).

4a

Appendix A

more readily determine whether a claim recites subject

matter that is an abstract idea.

Section II explains that the USPTO has set forth a

revised procedure, rooted in Supreme Court caselaw,

to determine whether a claim is “directed to” a judicial

exception under the first step of the Alice/Mayo test

(USPTO Step 2A).

Section III explains the revised procedure that will

be applied by the USPTO. The procedure focuses on two

aspects of Revised Step 2A: (1) Whether the claim recites

a judicial exception; and (2) whether a recited judicial

exception is integrated into a practical application. Only

when a claim recites a judicial exception and fails to

integrate the exception into a practical application, is the

claim “directed to” a judicial exception, thereby triggering

the need for further analysis pursuant to the second step of

the Alice/Mayo test (USPTO Step 2B). Finally, if further

analysis at Step 2B is needed (for example to determine

whether the claim merely recites well-understood, routine,

conventional activity), this 2019 Revised Patent Subject

Matter Eligibility Guidance explains that the examiner

or administrative patent judge will proceed in accordance

with existing USPTO guidance as modified in April 2018.6

6. USPTO Memorandum of April 19, 2018. “Changes in

Examination Procedure Pertaining to Subject Matter Eligibility,

Recent Subject Matter Eligibility Decision (Berkheimer v. HP, Inc.)”

(Apr. 19, 2018), available at https://www.uspto.gov/sites/default/files/

documents/memo-berkheimer-20180419.PDF [hereinafter “USPTO

Berkheimer Memorandum”).

5a

Appendix A

***

• an additional element that applies or uses

a judicial exception to effect a particular

treatment or prophylaxis for a disease or

medical condition;26

****

26. For example, an immunization step that integrates an

abstract idea into a specific process of immunizing that lowers the

risk that immunized patients will later develop chronic immunemediated diseases. See, e.g., Classen Immunotherapies, Inc. v.

Biogen IDEC, 659 F.3d 1057, 1066-68 (Fed. Cir. 2011). See also

Vanda Pharm. Inc. v. West-Ward Pharm. Int’l Ltd., 887 F.3d 1117,

1135 (Fed. Cir. 2018) (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 (USPTO Step 2A)), and USPTO Vanda

Memorandum (discussing Vanda).

6a

Appendix

B

APPENDIx B — UNITED

STATES

PATENT AND

TRADEMARk OFFICE AMENDMENT TO

NON-FINAL REjECTION

IN THE UNITED STATES PATENT

AND TRADEMARk OFFICE

Applicants(s): Curt D. Wolfgang, et al.

Conf. No.:

7411

Serial No.:

11/576,178

Art Unit:

1634

Filed:

March 28, 2007

Examiner:

Diana B. Johannsen

Examiner:

VAND-0002-US

Title:

Methods for the Administration of

Iloperidone

Date: March 20, 2013

Mail Stop Amendment

Commissioner for Patents

P.O. Box 1450

Alexandria, VA 22313 -1450

7a

Appendix B

AMENDMENT TO NON-FINAL REjECTION

Sir:

I. INTRODUCTORY COMMENTS

This paper is in response to the non-final Office

Action dated December 20, 2012. Please amend the abovereferenced patent application as follows:

The Amendments to the Claims are reflected in the

listing of the claims that begins on page 2 of this paper.

Remarks begin on page 7 of this paper.

The Conclusion appears on page 18 of this paper.

****

None of Jain, Woosley, or Neville cures or is alleged

to cure the above-discussed deficiencies in Obach. As

noted in the Office Action, “Jain does not teach the

administration of iloperidone to a subject who ‘is a

CYP2D6 poor metabolizer’ or to a subject who ‘is at

risk for iloperidone-induced QTc prolongation”’ (Office

Action, p. 6.) Rather, “Jain provides an overview of several

studies of iloperidone, teaching that daily dosages of

iloperidone up to 24 mg/day have been ‘found to be well

tolerated’ (citation omitted), as well as clinical trials in

which iloperidone was administered at dosages of 4 and

8 mg/day and at 0.25 - 3 mg b.i.d. (citation omitted). Jain

also discloses a long term study of dosages of 4-16 mg/day

8a

Appendix B

(citation omitted), as well as the finding of efficacy at a

dosage of 8 mg/day, and tolerance of a dosage of 32 mg/day

(citation omitted).” (Office Action, p. 5.) These teachings,

even in combination with Obach’s, fail to disclose or even

hint at the claimed methods, including “if the patient has

a CYP2D6 poor metabolizer genotype, then internally

administering iloperidone to the patient in an amount of

12 mg/day or less, and if the patient has a CYP2D6 normal

metabolizer genotype or a CYP2D6 extensive metabolizer

genotype, then internally administering iloperidone to

the patient in an amount that is greater than 12 mg/day,

up to 24 mg/day, wherein 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 than it would be if the iloperidone were administered

in an amount that is greater than 12 mg/day, up to 24

mg/day” (claim 63), “internally administering iloperidone

to [a patient who is suffering from a psychotic disorder

and is a CYP2D6 poor metabolizer] in an amount of up

to 12 mg/day” (claim 71), and “internally administering

iloperidone to [a patient who is suffering from a psychotic

disorder and who is at risk for iloperidone-induced QTc

prolongation] in an amount of up to 12 mg/day” (claim 77).

****