Cephalon, Inc. v. Abraxis Bioscience, LLC ( 2015 )

NOTE: This disposition is nonprecedential.
United States Court of Appeals
for the Federal Circuit
______________________
CEPHALON, INC., ACUSPHERE, INC.,
Plaintiffs-Appellants
v.
ABRAXIS BIOSCIENCE, LLC, CELGENE CORP.,
Defendants-Cross-Appellants
ABRAXIS BIOSCIENCE, INC.,
Defendant
______________________
2014-1411, 2014-1442
______________________
Appeals from the United States District Court for the
District of Massachusetts in No. 1:11-cv-12226-RGS,
Judge Richard G. Stearns.
______________________
Decided: June 17, 2015
______________________
GEORGE C. LOMBARDI, Winston & Strawn LLP,
Chicago, IL, argued for plaintiffs-appellants. Also
represented by WILLIAM P. FERRANTI, KARL LEONARD.
GREGORY A. CASTANIAS, Jones Day, Washington, DC,
argued for defendants-cross-appellants. Also represented
2 CEPHALON v. ABRAXIS
by JOHN PATRICK ELSEVIER, ANTHONY M. INSOGNA, PHILIP
T. SHENG, San Diego, CA; CHRISTOPHER M. MORRISON,
Boston, MA.
______________________
Before WALLACH, MAYER, and CHEN, Circuit Judges.
WALLACH, Circuit Judge.
Plaintiffs-appellants Acusphere, Inc. and Cephalon,
Inc. (collectively, “Acusphere”) appeal certain claim
construction determinations of the United States District
Court for the District of Massachusetts with respect to a
patent directed to formulations of, and methods of
making, the anticancer drug product paclitaxel. In light
of the district court’s construction, Acusphere stipulated
to a final judgment of non-infringement. Defendants-
cross-appellants Abraxis Bioscience, LLC and Celgene
Corp. (collectively, “Celgene”) cross-appeal, asserting
certain claim terms of the patent are indefinite. Because
the district court properly construed at least some of the
disputed terms, this court affirms and does not reach the
indefiniteness issues presented by the cross-appeal.
BACKGROUND
Acusphere, Inc. is the assignee of U.S. Reissued
Patent No. RE40,493 (“the ’493 patent”), titled “Porous
Paclitaxel Matrices and Methods of Manufacture
Thereof.” Acusphere, Inc., and its exclusive licensee
Cephalon, Inc., sued Celgene for infringement of the ’493
patent based on Celgene’s Abraxane drug product, which
contains a fast-dissolving form of paclitaxel.
Paclitaxel is a type of taxane compound derived from
the bark of the Pacific yew tree and exhibits “extremely
low solubility in water,” ’493 patent col. 1 ll. 22–27,
making effective administration challenging. The prior
art clinical formulation addressed this problem by the use
of a solubilizing agent called Cremophor
CEPHALON v. ABRAXIS 3
(polyoxyethylated castor oil), but this agent can cause
severe adverse reactions and requires infusion into the
patient over several hours. The ’493 patent addresses the
solubility problem by integrating paclitaxel into a “porous
matrix form which forms nanoparticles and microparticles
of paclitaxel when the matrix is contacted with an
aqueous medium.” Id. col. 1 l. 66–col. 2 l. 1.
Following the district court’s construction of a number
of disputed claim terms, see Cephalon, Inc. v. Celgene
Corp., 985 F. Supp. 2d 171 (D. Mass. 2013), Acusphere
stipulated to noninfringement. Acusphere appeals the
district court’s claim constructions of: (1) “nanoparticles”
and “microparticles”; (2) “nanoparticles and
microparticles of a taxane”; and (3) “wherein upon
exposure to an aqueous medium, the matrix dissolves to
leave the taxane nanoparticles and microparticles.” See
Appellants’ Br. 2–3. Acusphere stipulated that if any of
the district court’s claim constructions are affirmed, it
cannot sustain its burden of proving infringement of the
’493 patent. J.A. 29. This court has jurisdiction under 28
U.S.C. § 1295(a)(1) (2012).
DISCUSSION
I. Standard of Review
This court reviews the district court’s claim
construction de novo, but “review[s] for clear error those
factual findings that underlie a district court’s claim
construction.” Teva Pharm. USA, Inc. v. Sandoz, Inc., 135
S. Ct. 831, 841–42 (2015).
II. The District Court Correctly Construed
“Nanoparticles” and “Microparticles”
All asserted claims require a matrix formed of, among
other things, “nanoparticles” and “microparticles” of a
taxane. See, e.g., ’493 patent col. 12 l. 4. Claim 1 is
representative:
4 CEPHALON v. ABRAXIS
A pharmaceutical composition comprising a
porous matrix formed of a hydrophilic excipient, a
wetting agent and nanoparticles and
microparticles of a taxane, wherein the
nanoparticles and microparticles have a mean
diameter between about 0.01 and 5 µm and a total
surface area greater than about [0.5 m2] 0.5
m2/mL, wherein the porous matrix is in a dry
powder form, and wherein upon exposure to an
aqueous medium, the matrix dissolves to leave the
taxane nanoparticles and microparticles, wherein
the dissolution rate of the taxane nanoparticles
and microparticles in an aqueous solution is
increased relative to unprocessed taxane.
Id. col. 12 ll. 2–12 (first emphasis added; second emphasis
indicates an addition made upon reissue; brackets
indicate a deletion from the original patent).
The district court construed the term “nanoparticles”
to mean “particles that have a mean diameter of between
about 1 to 1000 nanometers and less than that of
microparticles,” and construed “microparticles” to mean
“particles that have a diameter of between about 1 to 1000
microns and greater than that of nanoparticles.” J.A. 28–
29; see also Cephalon, 985 F. Supp. 2d at 175–78. The
district court found these constructions supported by the
“widely accepted definition” of the terms nanoparticles
and microparticles. Cephalon, 985 F. Supp. 2d at 176. It
also found “that other Acusphere patents in the same
field, many credited to the inventors of the ’493 patent,”
define microparticles as ranging from 1 to 1000 microns
(µm) and nanoparticles as ranging from 1 to 1000
nanometers (nm). Id. The district court also looked to a
textbook, entitled Microparticulate Systems for the
Delivery of Proteins and Vaccines, which further
confirmed this understanding.
CEPHALON v. ABRAXIS 5
Acusphere first argues the “‘widely accepted
definition[s]’” of the disputed terms are “not standard
usage.” Appellants’ Br. 18 (quoting Cephalon, 985 F.
Supp. 2d at 176). As the United States Supreme Court
has recently instructed, “‘how the art underst[ands] [a]
term . . . [is] plainly a question of fact.’” Teva, 135 S. Ct.
at 838 (quoting Harries v. Air King Prods., Co., 183 F.2d
158, 164 (2d Cir. 1950) (Hand, C.J.)). Technical words
“may give rise to a factual dispute” that, “like all other
factual determinations, must be reviewed for clear error.”
Id. at 837–38. The terms “microparticles” and
“nanoparticles” are technical words, and how the relevant
scientific community understands them is therefore a
question of fact reviewable for clear error.
Acusphere fails to establish clear error. It asserts
“‘there is no universally agreed definition of the size of a
nanoparticle.’” Appellants’ Br. 20 (emphasis modified)
(quoting Cephalon, 985 F. Supp. 2d at 176). However, the
district court described its finding as to how the art
understood the terms nanoparticles and microparticles
not as “universal” but as “widely accepted.” Cephalon,
985 F. Supp. 2d at 176. To the extent Acusphere is
arguing the district court committed legal error by basing
its construction on an understanding that was less than
universally accepted, a definition need not be universally
accepted to form a proper basis for claim construction.
See Phillips v. AWH Corp., 415 F.3d 1303, 1314 (Fed. Cir.
2005) (en banc) (Claim construction may “involve[] little
more than the application of the widely accepted meaning
of commonly understood words.”) (emphasis added).
Furthermore, it was not clear error to credit Acusphere’s
other patents in the field or the textbook. 1 Moreover, we
1 It appears the district court understood the
relevant portion of the textbook to be co-authored by one
of the named inventors. Although this is incorrect, the
6 CEPHALON v. ABRAXIS
cannot find clear error given that Acusphere’s expert, Dr.
Robert Langer, 2 stated “the ordinary meanings of
‘nanoparticles’ and ‘microparticles’ are directed to particle
size, with ‘nanoparticles’ referring to particles with a
diameter in the nanometer (nm) range and
‘microparticles’ referring to particles with a diameter in
the micrometer (μm) range.” J.A. 1550 ¶ 28. In addition,
Celgene’s expert, Dr. Amiji, described the range of 1 to
1,000 nanometers for nanoparticles, and 1 to 1,000
microns for microparticles as “the accepted definition[s].”
J.A. 3100 ll. 5–8, 14–20.
Expert testimony, dictionaries, treatises, and other
extrinsic evidence that shed light on the commonly
understood meaning of a technical term are “less
significant than the intrinsic record in determining the
legally operative meaning of claim language.” Phillips,
415 F.3d at 1317 (internal quotation marks and citations
omitted). “[T]he specification may reveal a special
definition given to a claim term by the patentee that
differs from the meaning it would otherwise possess. In
such cases, the inventor’s lexicography governs.” Id. at
1316.
Drawing on this principle, Acusphere asserts the
inventors of the ’493 patent acted as their own
lexicographers of the terms “nanoparticles” and
“microparticles” by reciting in the claim itself
“nanoparticles and microparticles of a taxane, wherein
the nanoparticles and microparticles have a mean
diameter between about 0.01 and 5 µm.” Appellants’ Br.
district court’s recognition of the information in the
textbook was nevertheless not clear error.
2 Dr. Langer was also a founder of Acusphere and a
scientific advisor to it at the time of prosecution of the
application that led to the ’493 patent. See J.A. 3176 ll.
10–15, 3177 ll. 2–6.
CEPHALON v. ABRAXIS 7
21 (internal quotation marks and citation omitted).
However, this claim language requires the mean diameter
of the smaller nanoparticles and larger microparticles to
be between about 0.01 and 5 µm, and indicates the porous
matrix must include particles falling into both size
ranges. It does not provide any independent definition of
the terms “nanoparticles” or “microparticles.”
By providing only a single range (0.01 to 5 µm), the
language could, at most, define the size of either
nanoparticles or microparticles, unless the two terms are
construed to have no difference in meaning. Perhaps
recognizing this constraint, Acusphere proposes the two
terms should be construed as meaning exactly the same
thing, namely, “particles of a taxane having a mean
diameter between about 0.01 and 5 µm.” Appellants’ Br.
10. However, construing the two terms to have no
difference in meaning would render one of the terms
superfluous, which is disfavored in claim construction.
See Merck & Co. v. Teva Pharm. USA, Inc., 395 F.3d
1364, 1372 (Fed. Cir. 2005) (“A claim construction that
gives meaning to all the terms of the claim is preferred
over one that does not do so.”); Power Mosfet Techs.,
L.L.C. v. Siemens AG, 378 F.3d 1396, 1410 (Fed. Cir.
2004) (explaining that a claim construction that renders
claim terms superfluous is generally disfavored).
In addition, the prosecution history precludes
assigning the two terms the same meaning. The
predecessor to claim 1 originally recited only
“microparticles.” See J.A. 1016. A U.S. Patent and
Trademark Office examiner rejected the claims as obvious
in light of U.S. Patent Nos. 6,096,331 (“Desai”) and
5,855,913 (“Hanes”). In the rejection, the examiner stated
that, in view of these references, the use of micron-sized
particles would have been known to one having ordinary
skill in the art. In response, Acusphere stated “[t]here are
no nanoparticles” in Hanes. J.A. 1021. In the same
transmittal, it also amended claim 1 by, among other
8 CEPHALON v. ABRAXIS
things, substituting “nanoparticles and microparticles” in
place of “microparticles,” without altering the size range
of the particles (0.01 to 5 μm). See J.A. 1016. Under
Acusphere’s construction, a pharmaceutical composition
could incorporate only micron-sized particles and still fall
within the scope of the claims. Such a construction is
inconsistent with Acusphere’s amendment adding
“nanoparticles and” to overcome Hanes’s use of only
microparticles. Acusphere does not offer an explanation
of why the word “nanoparticles” was added during
prosecution, stating only “the inventors tweaked their
nomenclature” which it claims “was a matter of
semantics, not substance.” Appellants’ Br. 33–34. This
assertion, however, is unsupported by the prosecution
history.
Acusphere argues the district court’s construction of
microparticles is inconsistent with dependent claim 6,
which claims “[t]he composition of claim 1 wherein the
mean diameter of the taxane microparticles is between
about 0.50 and 5 μm.” ’493 patent col. 12 ll. 30–31. If
“microparticles” must have a minimum diameter of 1 µm,
Acusphere reasons, it would be impossible for the mean
diameter of a composition of such particles to be 0.50 µm,
as claim 6 requires. This inconsistency could perhaps be
explained by the addition elsewhere of the term
“nanoparticles” during prosecution, in combination with
an inadvertent failure to consistently amend the claims.
See Cephalon, 985 F. Supp. 2d at 177 n.2 (“Any
inconsistency, however, is a product of Acusphere’s at
times seemingly random omission of the term
‘nanoparticles’ in the patent.”).
In any event, the lexicography exception requires the
patent drafter to “‘clearly set forth a definition of the
disputed claim term.’” Aventis Pharma S.A. v. Hospira,
Inc., 675 F.3d 1324, 1330 (Fed. Cir. 2012) (quoting
Thorner v. Sony Computer Entm’t Am. L.L.C., 669 F.3d
1362, 1365 (Fed. Cir. 2012)). If, as Acusphere asserts, the
CEPHALON v. ABRAXIS 9
range of 0.01 to 5 µm specified in claim 1 constitutes a
definition of “microparticles,” it is unclear why nearly
identical language in claim 6 would not also constitute a
definition. However, claim 6 provides a different range of
0.50 to 5 µm, which would yield two different definitions
of “microparticles.” These inconsistent “definitions” do
not “clearly set forth a definition of the disputed claim
term” as required by this court’s precedent. Id. (emphasis
added) (internal quotation marks and citation omitted).
The district court therefore correctly construed the terms
“microparticles” as “particles that have a diameter of
between about 1 to 1000 micrometers and greater than
that of nanoparticles” and “nanoparticles” as “particles
that have a diameter of between about 1 to 1000
nanometers and less than that of microparticles.” J.A.
28–29.
Acusphere stipulated that under the district court’s
constructions of any one of the terms “nanoparticles,”
“microparticles,” “nanoparticles and microparticles of a
taxane,” or “wherein upon exposure to an aqueous
medium, the matrix dissolves to leave the taxane
nanoparticles and microparticles,” Acusphere cannot
sustain its burden of proving infringement of the ’493
patent. J.A. 29. Because this court affirms the district
court’s construction of “nanoparticles” and
“microparticles,” this court does not reach the
construction of the remaining terms. See Uship
Intellectual Props., LLC v. United States, 714 F.3d 1311,
1313 n.1 (Fed. Cir. 2013) (“Because construction of
‘validating’ resolves this case, we need not reach the
parties’ arguments with regard to ‘storing.’”).
CONCLUSION
For these reasons, the decision of the district court is
AFFIRMED