Document ID: s3://data.kl3m.ai/documents/govinfo/USCOURTS/USCOURTS-ca13-14-01411/USCOURTS-ca13-14-01411-0/pdf.json

Parties Involved:
Abraxis Bioscience, Inc.
Not party
Abraxis Bioscience, LLC
Cross-Appellant
Acusphere, Inc.
Appellant
Celgene Corp.
Cross-Appellant
Cephalon, Inc.
Appellant

Document Text:

NOTE: This disposition is nonprecedential.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 

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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. Defendantscross-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 

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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: 

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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. 

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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 

 

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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. 

 

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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 

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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 

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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

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