Sumitomo Dainippon Pharma Co. v. Emcure Pharmaceuticals , 887 F.3d 1153 ( 2018 )

United States Court of Appeals
for the Federal Circuit
______________________
SUMITOMO DAINIPPON PHARMA CO., LTD.,
SUNOVION PHARMACEUTICALS INC.,
Plaintiffs-Appellees
v.
EMCURE PHARMACEUTICALS LIMITED,
HERITAGE PHARMA LABS INC., FKA EMCURE
PHARMACEUTICALS USA INC., INVAGEN
PHARMACEUTICALS, INC., TEVA
PHARMACEUTICALS USA, INC., TEVA
PHARMACEUTICAL INDUSTRIES, LTD.,
Defendants-Appellants
______________________
2017-1798, 2017-1799, 2017-1800
______________________
Appeals from the United States District Court for the
District of New Jersey in Nos. 2:15-cv-00280-SRC-CLW,
2:15-cv-00281-SRC-CLW, 2:15-cv-06401-SRC-CLW, Judge
Stanley R. Chesler.
______________________
Decided: April 16, 2018
______________________
PRESTON K. RATLIFF, II, Paul Hastings LLP, New
York, NY, argued for plaintiffs-appellees. Also represent-
ed by JOSEPH M. O’MALLEY, JR.; STEPHEN BLAKE
KINNAIRD, Washington, DC; WILLIAM CHARLES BATON,
2 SUMITOMO DAINIPPON PHARMA CO. v. EMCURE PHARM. LTD.
CHARLES M. LIZZA, Saul Ewing Arnstein & Lehr LLP,
Newark, NJ.
CHRISTOPHER K. HU, Blank Rome LLP, New York,
NY, argued for all defendants-appellants. Defendants-
appellants Emcure Pharmaceuticals Limited, Heritage
Pharma Labs Inc. also represented by JAY PHILIP
LESSLER; DAVID C. KISTLER, Princeton, NJ.
ROBERT S. SILVER, Caesar, Rivise, Bernstein, Cohen &
Pokotilow, Ltd., Philadelphia, PA, for defendant-appellant
Invagen Pharmaceuticals, Inc. Also represented by
SALVATORE GUERRIERO, PEI-RU WEY.
IRA J. LEVY, Goodwin Procter LLP, New York, NY, for
defendants-appellants Teva Pharmaceuticals USA, Inc.,
Teva Pharmaceutical Industries, Ltd. Also represented
by LINNEA P. CIPRIANO, CYNTHIA LAMBERT HARDMAN;
WILLIAM M. JAY, Washington, DC; DAVID ZIMMER, Boston,
MA; BRIAN JOSEPH PREW, Greenberg Traurig, LLP, New
York, NY.
______________________
Before MOORE, MAYER, and STOLL, Circuit Judges.
STOLL, Circuit Judge.
This Hatch-Waxman appeal requires us to construe
the scope of a claim depicting a compound’s chemical
structure. Although the compound can exist in two differ-
ent three-dimensional orientations that are mirror images
of each other, only one is portrayed in the claim. The
district court construed the claim to cover the two three-
dimensional orientations in isolation—both the one shown
in the claim and its mirror image—as well as mixtures of
the two in any ratio. The parties then stipulated to
infringement and the entry of an injunction. We agree
that, at a minimum, the claim encompasses the specific
orientation depicted. Because this orientation is the
SUMITOMO DAINIPPON PHARMA CO. v. EMCURE PHARM. LTD. 3
active pharmaceutical ingredient in each party’s commer-
cial product, we need not determine what else falls within
the claim’s ambit to resolve the present dispute. We
affirm.
I
Stereochemistry is the study of a molecule’s three-
dimensional structure. Stereoisomers are molecules with
the same chemical formula and structure but different
three-dimensional configurations. If two stereoisomers
are non-superimposable mirror images of one another,
they are called enantiomers. Compounds with chiral
centers—a carbon atom bonded to four non-identical
atoms or groups of atoms—provide common examples of
compounds with enantiomers. Although enantiomers
often have identical physical properties, such as density
and boiling point, they can exhibit different pharmacolog-
ical properties in the human body.
When drawing enantiomers, chemists use wedges and
dashes to indicate the three-dimensional structure. A
wedge designates a bond coming out of the plane of the
paper towards the reader, a dashed line represents a bond
extending behind the plane of the paper, and normal lines
signify bonds in the same plane as the paper. A simple
example of two enantiomers is shown below:
4 SUMITOMO DAINIPPON PHARMA CO. v. EMCURE PHARM. LTD.
J.A. 1010. The two molecules are enantiomers because
they cannot be made identical to one another without
breaking and rearranging the chemical bonds. If the
molecule on the right is rotated to align atoms “1” and “2”
with the molecule on the left, atoms “3” and “4” are in the
reverse position.
Chemists often characterize enantiomers as “(+)” or
“(–)” based on their optical activity—the ability of a solu-
tion containing one enantiomer to rotate polarized light.
A solution of the (+)-enantiomer rotates the plane of
polarized light in a clockwise direction, and a solution of
the (–)-enantiomer rotates the plane of polarized light in a
counter-clockwise direction.
Mixtures can contain enantiomers in any ratio. A
mixture with 50% of the (+)-enantiomer and 50% of the
(–)-enantiomer is known as a “racemate” or “racemic
mixture.” Racemic mixtures do not rotate the plane of
polarized light because the clockwise rotation caused by
the (+)-enantiomer cancels out the equal but opposite
counter-clockwise rotation of the (–)-enantiomer.
Having summarized the relevant organic chemistry
principles, we now turn to the merits of this appeal.
Sumitomo Dainippon Pharma Co. and Sunovion Pharma-
ceuticals Inc. own U.S. Patent No. 5,532,372. The ’372
patent relates generally to “novel imide compounds and
their acid addition salts” that are useful as antipsychotic
agents. ’372 patent col. 1 ll. 8–12. The ’372 patent dis-
closes and claims more than one billion compounds, some
of which have stereo and optical isomers. Id. at col. 4
ll. 51–53. Lurasidone, the (–)-enantiomer of an imide
compound covered by the ’372 patent, is the active ingre-
dient in Sunovion’s schizophrenia and bipolar depression
drug LATUDA®.
The ’372 patent specification teaches several pre-
ferred embodiments in Examples 1(a) through 1(e).
SUMITOMO DAINIPPON PHARMA CO. v. EMCURE PHARM. LTD. 5
Example 1(a) describes the synthesis of Compound
No. 101, which the specification portrays as follows:
Id. at col. 30 ll. 40–65. Compound No. 101 is a chiral
molecule because it contains a cyclohexyl linker—the
region between the imide group on the left and the aryl-
piperazine group on the right—with two chiral centers.
The subsequent examples, 1(b) through 1(e), describe
methods for separating Compound No. 101 into its con-
stituent enantiomers in various salt forms. Examples 1(b)
and 1(c) detail the process for obtaining the
(+)-enantiomer (Compound No. 102) and (–)-enantiomer
(Compound No. 103), respectively, in the tartrate salt
form. See id. at col. 31 ll. 10–54. Examples 1(d) and 1(e)
then convert Compound Nos. 102 and 103 from the tar-
trate salt form to the hydrochloride salt form. Exam-
ple 1(d) produces the (+)-enantiomer (Compound No. 104),
and Example 1(e) creates the (–)-enantiomer (Compound
No. 105), which is lurasidone. See id. at col. 32 ll. 1–22.
After Emcure Pharmaceuticals Ltd., Heritage Pharma
Labs Inc., InvaGen Pharmaceuticals, Inc., Teva Pharma-
ceuticals USA, Inc., and Teva Pharmaceutical Industries,
Ltd. (collectively, “Appellants”) filed Abbreviated New
Drug Applications with the U.S. Food and Drug Admin-
istration seeking approval to market generic versions of
LATUDA®, Sumitomo and Sunovion sued the Appellants
for infringing claim 14 of the ’372 patent. Claim 14
recites:
6 SUMITOMO DAINIPPON PHARMA CO. v. EMCURE PHARM. LTD.
14. The imide compound of the formula:
or an acid addition salt thereof.
Just like depicted Compound No. 101, the claimed mole-
cule is chiral because of the two carbons in the cyclohexyl
linker. Both parties agree that the specific three-
dimensional structure depicted in claim 14 is lurasidone,
the (–)-enantiomer.
The claim construction question for the district court
centered on what combination of enantiomers claim 14
encompassed. Appellants sought to limit claim 14 to “a
racemic mixture of two enantiomers of which the struc-
tural formula is representative.” Sumitomo Dainippon
Pharma Co. v. Emcure Pharm. Ltd., No. CV 15-280, 2016
WL 6803077, at *2 (D.N.J. Nov. 15, 2016). For support,
Appellants relied on the claimed structure’s similarities to
Compound No. 101, which Appellants contend is a race-
mic mixture, organic chemistry textbooks suggesting that
ordinarily skilled artisans draw a single enantiomer as a
shorthand representation for a racemic mixture, and the
’372 patent’s prosecution history.
The district court rejected Appellants’ narrow con-
struction, which would have excluded the specific enanti-
omer depicted in claim 14. According to the court, even if
Compound No. 101 is a racemic mixture, its resemblance
to claim 14 did not justify importing that limitation from
the specification into the claim. The court also concluded
that the cited extrinsic evidence and prosecution history
were at best irrelevant and at worst contradictory to
Appellants’ construction. Therefore, the court adopted
SUMITOMO DAINIPPON PHARMA CO. v. EMCURE PHARM. LTD. 7
Sunovion’s proposal to construe claim 14 as covering
“lurasidone, lurasidone’s enantiomer, as well as mixtures
of these enantiomers.” Id. at *8.
Following the district court’s claim construction order,
Appellants stipulated to infringement of claim 14 and the
entry of permanent injunctions. Appellants then filed this
appeal. We have jurisdiction pursuant to 28 U.S.C.
§ 1295(a)(1).
II
Claim construction seeks to ascribe the “ordinary and
customary meaning” to claim terms as a person of ordi-
nary skill in the art would have understood them at the
time of invention. Phillips v. AWH Corp., 415 F.3d 1303,
1312–14 (Fed. Cir. 2005) (en banc) (quoting Vitronics
Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir.
1996)). As a general rule, the ordinary and customary
meaning controls unless “a patentee sets out a definition
and acts as his own lexicographer, or . . . the patentee
disavows the full scope of a claim term either in the
specification or during prosecution.” Thorner v. Sony
Comput. Entm’t Am. LLC, 669 F.3d 1362, 1365 (Fed. Cir.
2012). “While the ultimate construction of a claim term is
a legal question reviewed de novo,” underlying determina-
tions based on extrinsic evidence are factual determina-
tions that are reviewed for clear error when made by a
district court. Enzo Biochem Inc. v. Applera Corp.,
780 F.3d 1149, 1153 (Fed. Cir. 2015) (citing Teva Pharm.
USA, Inc. v. Sandoz, Inc., 135 S. Ct. 831, 841 (2015)).
As explained below, the plain claim language and
specification demonstrate that, at a minimum, claim 14
covers what it depicts: the (–)-enantiomer. This suffices
to resolve the parties’ dispute because Appellants concede
that the district court’s judgment can be affirmed if we
conclude that claim 14 at least covers the (–)-enantiomer.
See Oral Arg. at 8:40–9:10, http://oralarguments.
cafc.uscourts.gov/default.aspx?fl=2017-1798.mp3. We
8 SUMITOMO DAINIPPON PHARMA CO. v. EMCURE PHARM. LTD.
therefore express no opinion on the remainder of the
district court’s construction. See Vivid Techs., Inc. v. Am.
Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999)
(“[O]nly those terms need be construed that are in contro-
versy, and only to the extent necessary to resolve the
controversy.”).
The plain claim language marks the starting point for
our analysis. Phillips, 415 F.3d at 1312 (“[T]he claims are
‘of primary importance[] in the effort to ascertain precise-
ly what it is that is patented.’” (quoting Merrill v. Yeo-
mans, 94 U.S. 568, 570 (1876))). Claim 14 recites a
specific enantiomer and its acid addition salts. Both
parties agree that the structure shown in the claim is the
(–)-enantiomer; moreover, Appellants do not dispute that
a person of ordinary skill looking at claim 14’s structure
in a vacuum would understand it to be one way of depict-
ing the (–)-enantiomer. See Oral Arg. at 3:09–4:21,
http://oralarguments.cafc.uscourts.gov/default.aspx?fl=20
17-1798.mp3. Of equal importance is the lack of anything
in the claim language limiting its scope to a “racemate” or
“racemic mixture.” Absent some indication in the specifi-
cation or prosecution history to the contrary, it follows
that the plain and ordinary meaning of claim 14 covers at
least the specific enantiomer depicted in the claim itself.
The specification confirms our understanding of
claim 14’s plain and ordinary meaning. Instead of sug-
gesting that the (–)-enantiomer should be excluded, the
specification describes it as a preferred embodiment.
Although its structure is not shown, Example 1(e) details
the steps for obtaining Compound No. 105, the
(–)-enantiomer, from Compound No. 101 and even pro-
vides data on Compound No. 105’s physical properties.
See ’372 patent col. 32 ll. 18–22 (listing melting point and
optical rotation data). Accordingly, the intrinsic record
supports including the (–)-enantiomer—the specific enan-
tiomer that is displayed in the claim and described as a
preferred embodiment—within claim 14’s scope.
SUMITOMO DAINIPPON PHARMA CO. v. EMCURE PHARM. LTD. 9
This outcome comports with previous cases rejecting
similar attempts to limit claims to racemic mixtures.
Although differences in the patents’ specifications make it
such that they are not factually identical to the current
appeal, this does not detract from the convincing intrinsic
evidence we have required in cases confining otherwise-
unrestricted claims to racemic mixtures. For example, in
Pfizer, Inc. v. Ranbaxy Laboratories Ltd., Ranbaxy sought
to limit a claim depicting a specific three-dimensional
orientation to a racemic mixture. 457 F.3d 1284, 1288–89
(Fed. Cir. 2006). The compound at issue had four isomers:
R-trans, S-trans, R-cis, and S-cis. 1 The specification
disclaimed the R-cis and S-cis isomers, and it only dis-
closed reaction sequences that produced racemic mix-
tures. Ranbaxy argued that the specification’s disclosure,
combined with the convention that a racemate is often
represented by drawing one of the constituent enantio-
mers, justified limiting the claim to a racemic mixture.
We rejected these arguments because the claim itself
depicted the R-trans enantiomer, and unlike other claims
in the same patent, it was not limited by the “trans-(±)”
designation. Id. at 1289. And although the specification
disclaimed the two cis enantiomers, it did not include a
further disavowal that would constrain the patent’s scope
to a trans racemate. Therefore, we construed the claim to
cover the R- and S-trans enantiomers as well as any
mixtures of the two.
Appellants’ claim construction arguments conflict
with Pfizer and other precedent because they seek to
import limitations from the specification into the claim.
1 The “R” and “S” nomenclature is another way of
labeling a pair of enantiomers; the “trans” and “cis”
designations indicate whether the atom or group is on the
same or opposite side of a plane. Pfizer, 457 F.3d
at 1286–87.
10 SUMITOMO DAINIPPON PHARMA CO. v. EMCURE PHARM. LTD.
According to Appellants, Compound No. 101 is a racemic
mixture and claim 14’s scope should be coextensive with
Compound No. 101 because of the similarities in the
compounds’ structures. This argument relies on a series
of inferences. Appellants begin with the premise that
Compound No. 101 cannot be a pure enantiomer because
Examples 1(b)–(e) describe the process for separating
Compound No. 101 into the (+)- and (–)-enantiomers. See
’372 patent col. 31 l. 12 – col. 32 l. 22. The pure enantio-
mers of Compound Nos. 102–05 rotate the plane of polar-
ized light, as indicated by the patentees’ inclusion of
optical rotation data for these compounds. Id. at col. 31
𝐷𝐷 values for optical
ll. 22, 53; col. 32 ll. 12, 22 (listing [∝]25
activity). The ’372 patent, however, does not provide any
optical rotation data for Compound No. 101. Because the
’372 patent included optical rotation data for compounds
with optical activity, the absence of this data for Com-
pound No. 101 suggests that it lacks optical activity, i.e.,
it is a racemic mixture. Setting aside the particular salt
form of Compound No. 101, 2 its structure is identical to
claim 14, and thus Appellants assert that claim 14 should
be limited to a racemic mixture. Moreover, Appellants
argue that the specification’s treatment of Compound
Nos. 101–05 as distinct entities further supports their
contention that the structure in claim 14 depicts only
Compound No. 101 and not Compound Nos. 102–05.
In our view, the specification is inconclusive regard-
ing whether Compound No. 101 is a racemic mixture. The
specification does not refer to Compound No. 101 as a
“racemic mixture” or a “racemate”; indeed, those words do
not appear anywhere in the specification. While Com-
2 The “HCl” to the right of Compound No. 101’s
structure indicates that it is a hydrochloride salt.
See ’372 patent col. 30 ll. 40–65. The structure in claim
14 does not contain a similar indication.
SUMITOMO DAINIPPON PHARMA CO. v. EMCURE PHARM. LTD. 11
pound No. 101 does contain both the (+)- and
(–)-enantiomers, the ’372 patent sheds no light on the
relative ratio of each enantiomer present. Appellants’
inferences from the disparate reporting of optical data for
Compound Nos. 101–05 are not without merit, but we
need not decide this issue.
Even if Compound No. 101 is a racemic mixture, the
specification neither defines claim 14’s structure as Com-
pound No. 101 nor disclaims scope in a way that confines
claim 14 to a racemic mixture. See Thorner,
669 F.3d at 1367–68 (“Both [lexicography and disclaimer]
require a clear and explicit statement by the patentee.”).
To act as a lexicographer, the patentee must “clearly set
forth a definition of the disputed claim term.” CCS Fit-
ness, Inc. v. Brunswick Corp., 288 F.3d 1359, 1366 (Fed.
Cir. 2002). Here, the ’372 patent does not define the
structure in claim 14 as a racemate or as coextensive with
Compound No. 101. Claim 14 does not refer to Compound
No. 101, and nothing in the specification links the two
structures together. Compound No. 101 just happens to
be the only other place in the patent where claim 14’s
structure appears. This, of course, is not enough to re-
strict a claim’s scope. See, e.g., Johnson Worldwide As-
socs., Inc. v. Zebco Corp., 175 F.3d 985, 992 (Fed. Cir.
1999) (“[M]ere inferences drawn from the description of
an embodiment of the invention cannot serve to limit
claim terms.”).
The specification also does not disclaim the
(–)-enantiomer. For disclaimer, we look to the intrinsic
evidence for “expressions of manifest exclusion or re-
striction, representing a clear disavowal of claim scope.”
Teleflex, Inc. v. Ficosa N. Am. Corp., 299 F.3d 1313, 1325
(Fed. Cir. 2002). Our opinion in SciMed Life Systems, Inc.
v. Advanced Cardiovascular Systems, Inc., where we
concluded that the patentee disclaimed a dual lumen
configuration for balloon dilation catheters, is instructive.
242 F.3d 1337 (Fed. Cir. 2001). There, the patent de-
12 SUMITOMO DAINIPPON PHARMA CO. v. EMCURE PHARM. LTD.
scribed both a dual lumen (side-by-side) and coaxial
lumen configuration. The specification, however, dispar-
aged the dual lumen design, described the coaxial lumen
design as “the present invention,” and explained that the
coaxial lumen design was the structure “for all embodi-
ments of the present invention contemplated and dis-
closed herein.” Id. at 1342–44. We held that this
amounted to a disclaimer of the dual lumen configuration.
By contrast, nothing in the ’372 patent’s specification
disparages a specific enantiomer, refers to a racemic
mixture as forming the basis for the present invention, or
describes a racemic mixture as the basis for all of the ’372
patent’s embodiments. Finding no “expression[] of mani-
fest exclusion or restriction,” we cannot conclude that the
patentees disclaimed the (–)-enantiomer. See Teleflex,
Inc., 299 F.3d at 1325.
Finally, Appellants’ organic chemistry textbooks and
expert testimony do not compel a different result. Extrin-
sic evidence is, in general, “less significant than the
intrinsic record in determining ‘the legally operative
meaning of claim language.’” Phillips, 415 F.3d at 1317
(quoting C.R. Bard, Inc. v. U.S. Surgical Corp., 388 F.3d
858, 862 (Fed. Cir. 2004)). This is particularly so here,
where the intrinsic record demonstrates that claim 14’s
structure covers at least the (–)-enantiomer. See Vitronics
Corp., 90 F.3d at 1583 (“In most situations, an analysis of
the intrinsic evidence alone will resolve any ambiguity in
a disputed claim term. In such circumstances, it is im-
proper to rely on extrinsic evidence.”). In any event, we
see no clear error in the district court’s rejection of the
organic chemistry textbooks as irrelevant or contradictory
to Appellants’ construction. See Teva, 135 S. Ct. at 841.
And while Appellants’ expert contends that it is conven-
tional in the art to use a single enantiomer as shorthand
for a racemic mixture, he does not state that a person of
ordinary skill would always understand the depiction of a
SUMITOMO DAINIPPON PHARMA CO. v. EMCURE PHARM. LTD. 13
single enantiomer to exclude the very enantiomer depict-
ed. See J.A. 1015–16 ¶ 27.
III
We have considered the parties’ remaining arguments
and find them unpersuasive. The district court did not
err in construing claim 14 to cover the (–)-enantiomer.
Determining whether claim 14 covers additional scope is
unnecessary to the disposition of this appeal. The judg-
ment of the district court is affirmed.
AFFIRMED
COSTS
Costs to Appellees.