Reply Brief — Amarin Pharma, Inc., et al., Petitioners v. Hikma Pharmaceuticals USA Inc., et al.

No. 20-1119

IN THE

Supreme Court of the United States

AMARIN PHARMA, INC. AND

AMARIN PHARMACEUTICALS IRELAND LIMITED,

Petitioners,

v.

HIKMA PHARMACEUTICALS USA INC., HIKMA

PHARMACEUTICALS INTERNATIONAL LIMITED,

DR. REDDY’S LABORATORIES, INC., AND DR. REDDY’S

LABORATORIES, LTD.,

Respondents.

ON PETITION FOR A WRIT OF CERTIORARI TO THE

UNITED STATES COURT OF APPEALS

FOR THE FEDERAL CIRCUIT

REPLY BRIEF FOR PETITIONERS

MARK C. FLEMING

AMY R. PEARLMAN

WILMER CUTLER PICKERING

HALE AND DORR LLP

60 State Street

Boston, MA 02109

(617) 526-6000

JONATHAN E. SINGER

FISH & RICHARDSON P.C.

12390 El Camino Real

San Diego, CA 92130

(858) 678-5634

SETH P. WAXMAN

Counsel of Record

CLAIRE H. CHUNG

WILMER CUTLER PICKERING

HALE AND DORR LLP

1875 Pennsylvania Ave., NW

Washington, DC 20006

(202) 663-6000

seth.waxman@wilmerhale.com

TABLE OF CONTENTS

Page

TABLE OF AUTHORITIES ........................................... ii

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

ARGUMENT........................................................................ 3

I.

THE FEDERAL CIRCUIT’S PRIMA FACIE

FRAMEWORK CONFLICTS WITH THIS

COURT’S PRECEDENT ................................................... 3

II. THIS CASE PLAINLY RAISES THE

QUESTION PRESENTED ................................................ 6

III. THE REMAINING ISSUES ARE FOR LOWER

COURTS TO DECIDE ...................................................... 8

CONCLUSION ................................................................. 11

ii

TABLE OF AUTHORITIES

CASES

Page(s)

Goodyear Tire & Rubber Co. v. Ray-O-Vac Co.,

321 U.S. 275 (1944) ....................................................... 4

Graham v. John Deere Co. of Kansas City, 383

U.S. 1 (1966) .......................................................... 1, 3, 4

KSR International Co. v. Teleflex Inc., 550

U.S. 398 (2007) .................................................. 1, 4, 5, 6

Ohio Willow Wood Co. v. Alps South, LLC, 735

F.3d 1333 (Fed. Cir. 2013) ........................................... 4

Transocean Offshore Deepwater Drilling, Inc.

v. Maersk Drilling USA, Inc., 699 F.3d

1340 (Fed. Cir. 2012) .................................................... 4

RULES

Fed. Cir. R. 36 .............................................................. 2, 7, 8

INTRODUCTION

Amarin invested heavily to develop VASCEPA®—

its only drug on the market. No one had developed a

treatment for severe hypertriglyceridemia that does

not raise harmful LDL-C before Amarin, and yet the

lower courts found Amarin’s invention obvious by viewing the prior art in hindsight. That erroneous framework hinders research and innovation, as amici explained. The Court should grant certiorari, hold that

Graham’s totality framework governs, and restore

proper incentives for innovation. See Graham v. John

Deere Co. of Kansas City, 383 U.S. 1 (1966).

Respondents’ opposition misunderstands the totality framework this Court prescribed. Respondents repeatedly point to the district court’s statement that it

found obviousness “in view of all four Graham factors”

(Pet. App. 92a), which they argue shows a totality analysis. But the problem with the district court’s decision,

as Amarin explained, is that it found prima facie obviousness based solely on Graham’s technical factors and

only then turned to objective indicia to ask if they rebutted that finding. As dissenting Federal Circuit

judges have explained, such two-tiered analysis artificially diminishes the weight accorded to objective indicia and incorrectly shifts the burden to the patentee to

show nonobviousness. By contrast, Graham’s totality

framework requires consideration of all four factors together before making any obviousness determination,

so that objective indicia can effectively guard against

hindsight bias.

Respondents assert that KSR International Co. v.

Teleflex Inc., 550 U.S. 398 (2007), blessed the prima facie approach, but KSR did not even mention the prima

facie framework, and objective indicia were not at issue

2

in that case. To the extent the Court in KSR stated

that the prior art supported obviousness and the objective indicia did not dislodge that conclusion, that was

only because the Court was considering (and invalidating) a test that concerned the technical factors. After

all, KSR noted that any one Graham factor may be considered first, rejecting a mode of analysis that (like the

prima facie framework) always considers objective indicia last. And although respondents contend there is

no conflict within the Federal Circuit, Amarin never

argued an intra-circuit conflict. As Amarin explained,

the Federal Circuit has now settled on the prima facie

framework, which reinforces the need for this Court’s

review.

None of respondents’ purported vehicle issues presents an obstacle to certiorari. While respondents argue (Opp. 1) that the Federal Circuit’s summary affirmance “does not raise any issue at all,” this Court has

reviewed summary-affirmance cases, including recently

a Rule 36 judgment. See Pet. 30. Similarly, the district

court’s factual findings, including its statement that the

evidence of objective indicia was “weak” (Pet. App.

92a), have little relevance at this stage. The proper

Graham framework is a threshold legal issue in any obviousness inquiry and the only question presented here.

If the Court holds that the lower courts applied an incorrect framework, the remaining factual questions are

for the lower courts to decide on remand. Moreover,

the district court found objective indicia weak because

it viewed them through the wrong legal lens and allowed some of those indicia to undermine others, all

pursuant to the erroneous prima facie framework.

3

ARGUMENT

I.

THE FEDERAL CIRCUIT’S PRIMA FACIE FRAMEWORK

CONFLICTS WITH THIS COURT’S PRECEDENT

Respondents argue that the prima facie framework

is “consistent with both this Court’s and the Federal

Circuit’s precedent.” Opp. 25. But Graham, KSR, and

other decisions of this Court require consideration of all

Graham factors together before reaching any obviousness conclusion, instead of making a prima facie obviousness determination based solely on the technical factors and then considering objective indicia merely as

rebuttal. Pet. 18-21. The fact that the Federal Circuit

has now decided to consistently authorize the prima facie framework supports certiorari, because it shows

that the erroneous legal framework is here to stay absent this Court’s intervention.

A. Respondents argue that objective indicia may be

relegated to a second tier because the Court in Graham

called them “secondary considerations” that “might be

utilized” and “may have relevancy.” Opp. 26 (emphases

omitted). But the reference to “secondary” is not prescriptive. To the contrary, the Court emphasized that

objective indicia can play an important role that no other Graham factor can: they “‘guard against slipping into use of hindsight’” and “resist the temptation to read

into the prior art the teachings of the invention in issue.” Graham, 383 U.S. at 36. And while objective indicia obviously play no role when they are not present,

and may be more or less important depending on the

strength of the evidence, none of that suggests that,

where present, objective indicia are subsidiary to the

technical factors, as the Federal Circuit now holds.

Likewise, this Court’s observation that objective

indicia “should, in a close case, tip the scales in favor of

4

patentability,” Goodyear Tire & Rubber Co. v. Ray-OVac Co., 321 U.S. 275, 279 (1944) (quoted at Opp. 26),

does not diminish the relative importance of objective

indicia. As the Court explained in Graham, objective

indicia “give light to the circumstances surrounding the

origin” of the invention, including the technical factors.

383 U.S. at 17-18. In an ordinary case, therefore, objective indicia may illuminate whether the technical factors in fact present “a close case.” Graham’s totality

framework ensures a fair shake to objective indicia so

that they can tip the scales in favor of nonobviousness

in an appropriate case. Pet. 19-21. The prima facie

framework, by contrast, systematically disadvantages

objective indicia by limiting their role to rebuttal and

all but ensures that they will not matter. Pet. 22-24.

Indeed, the Federal Circuit has “rarely held” that evidence of objective indicia is “extensive” and thus “sufficient to overcome a prima facie case of obviousness.”

Transocean Offshore Deepwater Drilling, Inc. v.

Maersk Drilling USA, Inc., 699 F.3d 1340, 1354 (Fed.

Cir. 2012); see also Ohio Willow Wood Co. v. Alps

South, LLC, 735 F.3d 1333, 1344 (Fed. Cir. 2013).

KSR confirms the distinction between the totality

framework that Graham requires and the prima facie

framework that the Federal Circuit has now imposed.

Although the Court in KSR explained that the “the sequence of the[] questions” posed by Graham’s four factors may be “reordered” in any given case, 550 U.S. at

399, the prima facie framework predetermines that objective indicia will be considered last and only to rebut

an obviousness determination already made. Respondents misunderstand that fundamental incompatibility.

See Opp. 27. Even within the totality framework,

courts may well consider objective indicia last. What

contravenes this Court’s precedent is a two-tiered in-

5

quiry that determines prima facie obviousness first, before considering any objective indicia invariably as the

last step.1

Contrary to respondents’ argument (Opp. 26), KSR

did not apply “the same ‘framework’” as the Federal

Circuit now requires. As an initial matter, KSR nowhere mentions a prima facie framework. The question

there was whether the Federal Circuit may employ a

rigid “‘teaching, suggestion, or motivation’ test (TSM

test)” that required motivation or suggestion derived in

part from the technical factors to show obviousness.

550 U.S. at 407. The Court invalidated that test and

instead addressed the technical factors more holistically, which supported obviousness. Id. at 415, 422-426.

The Court then stated that “[l]ike the District Court,”

it concluded that the patent licensee had “shown no

secondary factors to dislodge” its obviousness determination. Id. at 426.

The Court’s phrasing in no way opined on—much

less minimized—the role of objective indicia, which

were not at issue in KSR. Rather, the opinion’s wording reflected the fact that it reviewed and invalidated

the TSM test, which concerned the technical factors.

The Court thus focused on those factors in order to

show how they should be considered instead of the

TSM test. The statement regarding objective indicia

merely agreed with the district court that there were

no valid objective indicia, an observation necessary to

find obviousness (see Opp. 28). The Court nowhere authorized the Federal Circuit’s prima facie framework,

especially given that the Court warned against hind1

For similar reasons, respondents’ argument (Opp. 27) that

Amarin waived its KSR argument by listing objective indicia last

in its district court post-trial briefing is meritless.

6

sight bias and explained that any one Graham factor

may be considered first. See 550 U.S. at 407, 421.

B. Respondents argue bizarrely there is no “relevant conflict within the Federal Circuit.” Opp. 27. But

that is just the problem—despite well-founded misgivings about the prima facie framework years ago, the

Federal Circuit has now made up its mind and the prima facie framework has become the rule. Pet. 21-24.

Contrary to respondents’ view, the difference between the prima facie framework and the totality

framework is not just “semantic” (Opp. 28-29).2 Respondents do not appear to dispute that the legal

framework affects the outcome of the analysis or that

the prima facie framework leads to over-invalidation of

patents. See Pet. 28-30. In any event, the fact that this

Court has found patentability based on objective indicia

in prior cases (Pet. 19-21), whereas the Federal Circuit

(by its own admission) rarely has, shows how consequential the prima facie framework can be in an obviousness inquiry.

II. THIS CASE PLAINLY RAISES THE QUESTION PRESENTED

A. This case undoubtedly presents the permissibility of the prima facie framework. The district court

was first “persuaded” of prima facie obviousness based

solely on the technical factors; only then did it turn to

objective indicia to see if they rebutted that determina2

Contrary to respondents’ assertion (Opp. 28), Amarin did

not agree that the use of a prima facie framework is “a question of

semantics, not substance.” What Amarin noted is that courts

could follow Graham’s framework where they consider all factors

before making any obviousness determination, even if they nominally use the language of a prima facie case. See C.A. Opening Br.

44-45; C.A. Reply Br. 3. That is not what the district court did

here.

7

tion. Pet. App. 75a-76a, 81a; see Pet. 14-15. In fact, it

could not have been clearer that the district court addressed objective indicia separately from the technical

factors—contrary to Graham’s totality framework—

because the court found that VASCEPA’s satisfaction

of a long-felt but unmet need and commercial success

were “outweighed by” certain “other proffered secondary considerations.” Pet. App. 92a. Plainly, the court

considered objective indicia to be a category unto

themselves wherein different considerations may undermine each other, rather than each objective consideration directly contributing to the overall obviousness

determination as other Graham factors would. Pet. 2627.

Respondents assert (Opp. 21) that the district court

applied Graham’s totality framework because it “reserved its conclusion of obviousness until after reviewing ‘all four Graham factors,’” but the district court’s

decision contradicts that view. The court’s concluding

statement that Amarin’s invention was obvious “in

view of all four Graham factors” (Pet. App. 92a) does

not refute the district court’s adherence to the prima

facie framework. The court determined that Amarin’s

invention was prima facie obvious based solely on Graham’s technical factors, and then found that the objective indicia did not rebut that determination, resulting

in the very problems that dissenting Federal Circuit

judges have identified. See Pet. 22-24. Those are not

“the same legal standards that Amarin asks this Court

to uphold.” Opp. 20.

B. Respondents’ broad assertion (Opp. 18) that the

Federal Circuit’s Rule 36 judgment “does not implicate

any question at all” is untenable. By that standard, the

Federal Circuit could insulate its decisions from this

Court’s review simply by issuing summary affirmances,

8

which it does in about 30% of its cases. See Pet. 30-31.

Understandably, the Court has not adopted such a categorical rule, having granted review in summaryaffirmance cases including where the Federal Circuit

issued a Rule 36 judgment (see Pet. 30)—none of which

respondents address. And respondents’ related argument (Opp. 18) that summary affirmance cannot “‘signal’ anything” because it is not precedential has it

backwards. As Amarin explained (Pet. 30), the Federal

Circuit’s apparent belief that its decision would have

“no precedential value,” Fed. Cir. R. 36(a), shows that

the court will not revisit the permissibility of the prima

facie framework on its own, thus confirming that the

issue is ripe for this Court’s intervention.

There is nothing objectionable about Amarin’s “vacate and remand” request either. In the event the

Court determines that the lack of a Federal Circuit

opinion somehow presents an obstacle to granting review, the Court should vacate and remand with instructions on Graham’s totality framework. Pet. 31. That

alternative request is no more “micromanagement”

(Opp. 19) than what this Court has done in prior cases.

Pet. 31 (citing cases).

III. THE REMAINING ISSUES ARE FOR LOWER COURTS TO

DECIDE

Respondents contend that applying Graham’s totality framework would not change the outcome because the district court made various factual findings

that respondents believe would support obviousness at

any rate. Opp. 22-25. In the first place, the existence of

factual issues is no ground to deny review. If the Court

holds the prima facie framework impermissible (a

threshold legal issue and the only question presented

here), it is for the lower courts to apply the proper

9

framework on remand, including by revising any factual findings as appropriate.3 It makes particularly little

sense for certiorari to depend on a factual issue that the

district court (or the Federal Circuit) did not address,

such as whether VASCEPA’s commercial success

lacked nexus to the patent claims. Opp. 24-25.

In any event, respondents are wrong on the merits.

Respondents argue (Opp. 22-24) that this was not a

close case because the district court found that the

technical factors supported obviousness and deemed

objective indicia to be “weak” (Pet. App. 92a). But the

court’s conclusion that the prior art supported obviousness was possible only by viewing the prior art in hindsight without regard for objective indicia. For instance, the objective evidence showed that no one had

developed a treatment for severe hypertriglyceridemia

that does not raise LDL-C, despite the asserted prior

art teachings. Pet. 25-26. Moreover, the court concluded that objective indicia were “weak” only because it

allowed its prima facie obviousness finding to devalue

objective indicia. For example, the court found that the

long-felt but unmet need for VASCEPA only “slightly”

favored nonobviousness because the improvement that

Amarin’s invention represented was “a prima facie obvious one.” Pet. App. 89a (emphasis added). The court

then exacerbated the problem by allowing objective indicia to cancel each other out. Pet. App. 88a-92a. Respondents’ argument (Opp. 29) that the district court’s

statement adopting that approach is “a single sentence

out of context” is flatly wrong. Under the heading

“Weighing These Secondary Considerations,” the court

3

Just because Amarin seeks review of the prima facie framework does not mean it “abandoned” (Opp. 22-23) other arguments

that may be relevant on remand.

10

stated that the objective indicia it found were “outweighed” by “other proffered secondary considerations” that it disagreed with and “[t]hus, at best, [Amarin] ha[s] presented weak evidence of the existence of

secondary considerations, which do not overcome the

Court’s finding that all Asserted Claims are prima facie

obvious.” Pet. App. 91a-92a. The “context” speaks for

itself.4

There is also no basis to discount VASCEPA’s

commercial success. See Opp. 24-25. If anything, the

fact that a large portion of VASCEPA’s sales comes

4

Respondents’ Statement is replete with one-sided and often

misleading characterizations of the record. For example, although

respondents state (Opp. 8, 14) that “at least five prior-art studies

on pure EPA included patients with” severe hypertriglyceridemia,

none involved populations with severe hypertriglyceridemia.

They were thus inadequate to form conclusions about EPA’s effects on those populations, as respondents’ own expert admitted.

C.A.J.A. 1398-1399. Respondents’ focus on Lavin’s declaration

(Opp. 13-14) is likewise a distraction. The Examiner did not rely

on his declaration (C.A.J.A. 88046-88053), and respondents’ expert

admitted that Hayashi—the subject of Lavin’s declaration—was

“not telling us anything about the effect of EPA on LDL-C values

in severely hypertriglyceridemic patients” (C.A.J.A. 1493-1494).

Respondents also rely on an email from Dr. Bays to argue that the

results of Amarin’s clinical trial (the MARINE study) were not

unexpected (Opp. 12), contrary to a statement in Dr. Bays’s own

published article that the results were unexpected (C.A.J.A.

90096). But Dr. Bays testified that he was unsure of what he

meant in the email, which predated his peer-reviewed article, because his “expectation was, prior to getting the results of the MARINE trial … that the LDL cholesterol levels would rise after

administration of [EPA] in patients with very high triglyceride

levels” (C.A.J.A. 3437-3439, 3445-3447, 48679). Finally, none of

Amarin’s supposed “concessions” (Opp. 15-16) changes the key

point that there was no reasonable expectation of success that

EPA would avoid LDL-C increase in patients with severe hypertriglyceridemia, which respondents were required to prove to establish obviousness.

11

from patients with triglyceride levels below 500 mg/dL

(i.e., not “very high” or “severe”) supports nonobviousness. As Amarin explained below, healthcare providers

typically have the option, based on their medical judgment, to prescribe drugs that (like VASCEPA) treat

very high levels of triglycerides to patients with lower

triglyceride levels. C.A.J.A. 103303. Had Amarin’s invention been obvious, other pharmaceutical companies

would have been induced to bring a drug like VASCEPA to market sooner because of the potential for considerable sales to patients with very high and lower

triglyceride levels. Id. But they did not. In any event,

even VASCEPA’s net sales to only those patients with

severe hypertriglyceridemia have increased sixfold

since VASCEPA’s launch, further supporting the nexus between VASCEPA’s commercial success and the

asserted claims. C.A.J.A. 103303, 2189.

CONCLUSION

The petition for a writ of certiorari should be

granted.

12

Respectfully submitted.

MARK C. FLEMING

AMY R. PEARLMAN

WILMER CUTLER PICKERING

HALE AND DORR LLP

60 State Street

Boston, MA 02109

(617) 526-6000

JONATHAN E. SINGER

FISH & RICHARDSON P.C.

12390 El Camino Real

San Diego, CA 92130

(858) 678-5634

JUNE 2021

SETH P. WAXMAN

Counsel of Record

CLAIRE H. CHUNG

WILMER CUTLER PICKERING

HALE AND DORR LLP

1875 Pennsylvania Ave., NW

Washington, DC 20006

(202) 663-6000

seth.waxman@wilmerhale.com