Wyeth & Cordis Corp. v. Abbott Laboratories

United States Court of Appeals
for the Federal Circuit
______________________
WYETH AND CORDIS CORPORATION,
Plaintiffs/Counterclaim Defendants-Appellants,
v.
ABBOTT LABORATORIES, ABBOTT
CARDIOVASCULAR SYSTEMS, INC., AND ABBOTT
LABORATORIES, INC.,
Defendants Counterclaimants-Appellees,
AND
MEDTRONIC INC., MEDTRONIC VASCULAR, INC.,
AND MEDTRONIC USA, INC.,
Defendants/Counterclaimants-Appellees,
AND
BOSTON SCIENTIFIC CORPORATION AND
BOSTON SCIENTIFIC SCIMED, INC.,
Defendants/Counterclaimants-Appellees.
______________________
2012-1223,-1224
______________________
Appeals from the United States District Court for the
District of New Jersey in No. 08-CV-0230, Judge Joel A.
Pisano.
______________________
Decided: June 26, 2013
______________________
2 WYETH v. ABBOTT LABORATORIES
DAVID T. PRITIKIN, Sidley Austin, LLP, of Chicago, Il-
linois, argued for plaintiffs/counterclaim defendants-
appellants. With him on the brief were CONSTANTINE L.
TRELA, JR., WILLIAM H. BAUMAGARTNER, JR., and RUSSELL
E. CASS. Of counsel on the brief was BRYAN C. MULDER.
EDWARD A. MAS, II, McAndrews, Held & Malloy, Ltd.,
of Chicago, Illinois, argued for Defend-
ants/Counterclaimants-Appellees Abbott Laboratories, et
al. With him on the brief were SANDRA A. FRANTZEN,
STEPHANIE F. SAMZ and KATHLEEN A. DORTON. Of counsel
on the brief was SAMUEL F. BAXTER, McKool Smith, P.C.,
of Dallas, Texas.
MATTHEW M. WOLF, Arnold & Porter, LLP, of Wash-
ington, DC, argued for defendants/counterclaimants-
appellees Boston Scientific Corporation, et al. With him
on the brief were EDWARD HAN and JOHN E. NILSSON.
______________________
Before MOORE, BRYSON, and WALLACH, Circuit Judges.
MOORE, Circuit Judge.
Wyeth and Cordis Corporation (Wyeth) appeal from
the U.S. District Court for the District of New Jersey’s
grant of summary judgment that claims 1 and 2 of U.S.
Patent No. 5,516,781 (’781 patent) and claim 1 of U.S.
Patent No. 5,563,146 (’146 patent) are invalid for nonena-
blement. 1 Wyeth v. Abbott Labs., Nos. 3:08-cv-0230 and -
1 Wyeth also appeals from the court’s grant of sum-
mary judgment that the claims are invalid for lack of
written description based on the “rapamycin” limitation,
and invalid for lack of written description and nonena-
blement based on another limitation. In light of our
holding on nonenablement with respect to the “rapamy-
cin” limitation, we need not reach these other issues.
WYETH v. ABBOTT LABORATORIES 3
1021, 2012 WL 175023 (D.N.J. Jan. 19, 2012). Because
we hold that there is no genuine issue of material fact
that the specification does not enable one of ordinary skill
to practice the asserted claims without undue experimen-
tation, we affirm.
BACKGROUND
The patents-in-suit relate to the use of rapamycin for
the treatment and prevention of restenosis, which is the
renarrowing of an artery. To open a blocked artery, a
physician guides a balloon catheter to the site of accumu-
lated plaque, and then inflates the balloon to crush the
plaque. As the balloon inflates, however, it may cause
injury to the arterial wall. That vascular injury causes
smooth muscle cells to proliferate, which thickens the
arterial wall, and, in turn, leads to restenosis.
The claims recite a method of treating or preventing
“restenosis in a mammal . . . which comprises administer-
ing an antirestenosis effective amount of rapamycin to
said mammal.” ’781 patent, claims 1 and 2; ’146 patent,
claim 1. In general, “rapamycin” may refer to a class of
compounds. While the patents-in-suit use the term
“rapamycin,” the parties agree that the shared specifica-
tion discloses only one rapamycin species called sirolimus.
Sirolimus is naturally produced by a bacterium called
Streptomyces hygroscopicus. The structure of sirolimus
appears below and includes a substituent group at and
beyond the C–37 position (dashed circle) and a macrocy-
clic triene ring (macrocyclic ring) indicated by the C–1 to
C–36 positions.
4 WYETH v. ABBOTT LABORATORIES
The parties do not dispute that the effective filing
date of both patents is January 9, 1992. At that time, it
was known that sirolimus acts in part by binding two
proteins at sites within the macrocyclic ring. It was also
known that there were four additional compounds with
the same macrocyclic ring as sirolimus, but different
substituent groups beyond the C–37 position.
The parties also do not dispute that the specification
discloses the immunosuppressive and antirestenotic
properties of sirolimus. The specification discloses in
vitro test data indicating that sirolimus inhibits rat
smooth muscle cell proliferation. See ’781 patent col. 5 l.
1–col. 6 l. 2. It also discloses in vivo test data indicating
that intraperitoneal injection of sirolimus in rats reduced
the thickening of the arterial wall following vascular
injury. See id. col. 6 ll. 39–65, col. 8 l. 17–col. 10 l. 16.
In two separate actions, Wyeth sued the defendants
for infringement of the patents-in-suit. The defendants
market stent products that elute everolimus and zotaro-
limus, two drugs that have the same macrocyclic ring as
sirolimus but different substituents at the C–42 position.
After briefing and a hearing, the district court adopted
Wyeth’s proposed construction of “rapamycin” as “a com-
pound containing a macrocyclic triene ring structure
produced by Streptomyces hygroscopicus, having immuno-
suppressive and anti-restenotic effects.” Wyeth, 2012 WL
175023, at *3. Based in part on that construction, the
WYETH v. ABBOTT LABORATORIES 5
court granted defendants’ joint motions for summary
judgment of invalidity for nonenablement and lack of
written description. Id. at *17–18. Wyeth appeals. We
have jurisdiction under 28 U.S.C. § 1295(a)(1).
DISCUSSION
I.
We review a grant of summary judgment under the
law of the regional circuit. Grober v. Mako Prods., Inc.,
686 F.3d 1335, 1344 (Fed. Cir. 2012). The Third Circuit
reviews a grant of summary judgment without deference.
Healy v. New York Life Ins. Co., 860 F.2d 1209, 1210 (3d
Cir. 1988). Summary judgment is appropriate if “the
movant shows that there is no genuine dispute as to any
material fact and the movant is entitled to judgment as a
matter of law.” FED. R. CIV. P. 56(a). “The evidence of the
nonmovant is to be believed, and all justifiable inferences
are to be drawn in his favor.” Anderson v. Liberty Lobby,
Inc., 477 U.S. 242, 255 (1986).
A patent’s specification must describe the invention
and “the manner and process of making and using it, in
such full, clear, concise, and exact terms as to enable any
person skilled in the art to which it pertains . . . to make
and use the same.” 35 U.S.C. § 112(a) (2012). Claims are
not enabled when, at the effective filing date of the pa-
tent, one of ordinary skill in the art could not practice
their full scope without undue experimentation. MagSil
Corp. v. Hitachi Global Storage Techs., Inc., 687 F.3d
1377, 1380– 81 (Fed. Cir. 2012). Enablement is a ques-
tion of law based on underlying facts. Id.
II.
The central issue on appeal is whether practicing the
full scope of the claims requires excessive—and thus
undue—experimentation. The district court held that it
does. Wyeth, 2012 WL 175023, at *17–18. It found that
the claims cover any structural analog of sirolimus that
exhibits immunosuppressive and antirestenotic effects.
6 WYETH v. ABBOTT LABORATORIES
Id. The court also found that, while the specification
describes assays to ascertain whether a potential rapamy-
cin compound exhibits the recited functional effects, the
only species disclosed is sirolimus. Id. In further support
of its holding of nonenablement, the court relied on the
unpredictability of the chemical arts, the complexity of
the invention, and the limited knowledge of treatment of
restenosis using sirolimus at the time of the invention.
Id.
Wyeth argues that the district court ignored evidence
that practicing the full scope of the claims would have
required only routine experimentation. It contends that
the claims do not cover a new genus of compounds, but
rather a new use for an existing class of compounds.
Wyeth argues that its experts opined that one of ordinary
skill would readily know how to practice the full scope of
the claims using two steps. First, a skilled artisan could
ascertain whether a candidate rapamycin compound has
the same macrocyclic ring as sirolimus. Second, a skilled
artisan could routinely determine whether a candidate
has immunosuppressive and antirestenotic effects using
the assays disclosed in the specification.
Regarding the amount of experimentation, Wyeth
acknowledges that one of its experts testified that there
could be millions of compounds made by varying the
substituent groups outside of sirolimus’s macrocyclic ring.
Wyeth counters that the same expert testified that the
number of compounds that would exhibit the recited
functional effects would be significantly smaller. Accord-
ing to Wyeth’s expert, one of ordinary skill would have
understood two relevant facts. First, in order to exhibit
the recited functional effects, a compound must be perme-
able across cell membranes. Second, such permeability
typically occurs in compounds having molecular weights
below 1,000–1,200 Daltons (sirolimus’s molecular weight
is approximately 914 Daltons), which further limits the
universe of potential rapamycin compounds.
WYETH v. ABBOTT LABORATORIES 7
Appellees respond that practicing the full scope of the
claims would have required excessive experimentation,
even if routine. They argue that the specification is silent
on how to structurally modify sirolimus to yield a com-
pound having the recited functional effects. Appellees
disagree that one of ordinary skill would have known to
select only compounds with a molecular weight below
1,200 Daltons. Even accepting Wyeth’s molecular weight
argument, however, Appellees respond that there are still
tens of thousands of potential compounds that require
screening. They emphasize that Wyeth’s own witnesses
testified that even minor alterations to the sirolimus
molecule could impact its immunosuppressive and an-
tirestenotic properties. Appellees argue that one of ordi-
nary skill would thus need, at a minimum, to engage in a
laborious iterative process to determine what candidates
fall within the claimed genus, and that there is no contra-
ry evidence in the record.
We agree with Appellees and the district court that
there is no genuine dispute that practicing the full scope
of the claims, measured at the time of filing, would re-
quire excessive experimentation. The scope of the claims
at issue is broad. Under the district court’s unchallenged
construction of “rapamycin,” the invention is a new meth-
od of use of a known compound (sirolimus) and any other
compounds that meet the construction’s structural and
functional requirements. We also agree that there is no
genuine dispute that the specification’s guidance is lim-
ited to disclosures of the immunosuppressive and an-
tirestenotic properties of sirolimus and assays to screen
for those properties. Wyeth attempts to broaden the
background knowledge in the art. It asserts, based in
part on expert testing performed in the course of litiga-
tion, that the four compounds known to have the same
macrocyclic ring as sirolimus at the effective filing date all
“have immunosuppressive and antirestenotic effects.”
Appellants’ Br. at 14 (emphasis added).
8 WYETH v. ABBOTT LABORATORIES
For purposes of summary judgment, we accept as true
Wyeth’s claims about the state of the art. We also accept
Wyeth’s expert testimony that one of ordinary skill would
have understood that potential rapamycin compounds
should have molecular weights below 1,200 Daltons in
order to be permeable across cell membranes. We also
accept as true that one of ordinary skill could routinely
use the assays disclosed in the specification to determine
immunosuppressive and antirestenotic effects in candi-
date compounds. Yet, even accepting Wyeth’s assertions,
we find no genuine dispute that practicing the full scope
of the claims would require more than routine experimen-
tation for two reasons.
First, there is no dispute that, even if potential ra-
pamycin compounds must have a molecular weight below
1,200 Daltons, there are still at least tens of thousands of
candidates. The specification is silent about how to
structurally modify sirolimus, let alone in a way that
would preserve the recited utility. Second, there is no
genuine dispute that it would be necessary to first syn-
thesize and then screen each candidate compound using
the assays disclosed in the specification to determine
whether it has immunosuppressive and antirestenotic
effects. There is no evidence in the record that any par-
ticular substitutions outside of the macrocyclic ring are
preferable. Indeed, a Wyeth scientist confirmed the
unpredictability of the art and the ensuing need to assay
each candidate by testifying that, “until you test [com-
pounds], you really can’t tell whether they work or not
[i.e., have antirestenotic effects].” J.A. 6929. In sum,
there is no genuine dispute that practicing the full scope
of the claims would require synthesizing and screening
each of at least tens of thousands of compounds.
The remaining question is whether having to synthe-
size and screen each of at least tens of thousands of
candidate compounds constitutes undue experimentation.
We hold that it does. Undue experimentation is a matter
of degree. Chiron Corp. v. Genentech, Inc., 363 F.3d 1247,
WYETH v. ABBOTT LABORATORIES 9
1253 (Fed. Cir. 2004) (internal quotation omitted). Even
“a considerable amount of experimentation is permissi-
ble,” as long as it is “merely routine” or the specification
“provides a reasonable amount of guidance” regarding the
direction of experimentation. Johns Hopkins Univ. v.
CellPro, Inc., 152 F.3d 1342, 1360–61 (Fed. Cir. 1998)
(internal quotation omitted). Yet, routine experimenta-
tion is “not without bounds.” Cephalon, Inc. v. Watson
Pharm., Inc., 707 F.3d 1330, 1339 (Fed. Cir. 2013).
Our cases have described limits on permissible exper-
imentation in the context of enablement. For example, in
ALZA Corp. v. Andrx Pharmaceuticals, LLC, we affirmed
a judgment of nonenablement where the specification
provided “only a starting point, a direction for further
research.” 603 F.3d 935, 941 (Fed. Cir. 2010) (internal
quotation omitted). We concluded that one of ordinary
skill “would have been required to engage in an iterative,
trial-and-error process to practice the claimed invention
even with the help of the . . . specification.” Id. at 943. In
Cephalon, although we ultimately reversed a finding of
nonenablement, we noted that the defendant had not
established that required experimentation “would be
excessive, e.g., that it would involve testing for an unrea-
sonable length of time.” 707 F.3d at 1339 (citing White
Consol. Indus., Inc. v. Vega Servo-Control, Inc., 713 F.2d
788, 791 (Fed. Cir. 1983)). Finally, in In re Vaeck, we
affirmed the PTO’s nonenablement rejection of claims
reciting heterologous gene expression in as many as 150
genera of cyanobacteria. 947 F.2d 488, 495–96 (Fed. Cir.
1991). The specification disclosed only nine genera,
despite cyanobacteria being a “diverse and relatively
poorly understood group of microorganisms,” with unpre-
dictable heterologous gene expression. Id. at 496.
Here, the specification similarly discloses only a start-
ing point for further iterative research in an unpredicta-
ble and poorly understood field. Synthesizing candidate
compounds derived from sirolimus could, itself, require a
complicated and lengthy series of experiments in synthet-
10 WYETH v. ABBOTT LABORATORIES
ic organic chemistry. Even putting the challenges of
synthesis aside, one of ordinary skill would need to assay
each of at least tens of thousands of candidates. Wyeth’s
expert conceded that it would take technicians weeks to
complete each of these assays. The specification offers no
guidance or predictions about particular substitutions
that might preserve the immunosuppressive and an-
tirestenotic effects observed in sirolimus. The resulting
need to engage in a systematic screening process for each
of the many rapamycin candidate compounds is excessive
experimentation. We thus hold that there is no genuine
dispute that practicing the full scope of the claims, meas-
ured at the filing date, required undue experimentation.
We have considered the remainder of Wyeth’s argu-
ments and do not find them to be persuasive. Because we
find no genuine dispute that the asserted claims are not
enabled, we affirm.
AFFIRMED