CELGENE CORPORATION v. NATCO PHARMA LIMITED

Filing 312

MARKMAN OPINION. Signed by Judge Susan D. Wigenton on 5/27/14. (jd, )

NOT FOR PUBLICATION
UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF NEW JERSEY

CELGENE CORPORATION,
Plaintiff,

Civil
(SDW)

Action

No.

10-5197

v.
MARKMAN OPINION
NATCO PHARMA LIMITED, ARROW
INTERNATIONAL LIMITED, AND
WARSON LABORATORIES, INC.

May 27, 2014

Defendants.

WIGENTON, District Judge.
Before the Court are the briefs and supporting materials of Plaintiff Celgene Corporation
(“Celgene”) and Defendants Natco Pharma Limited (“Natco”), Arrow International Limited
(“Arrow”), and Watson Laboratories, Incorporated (“Watson”) (collectively “Defendants”)
regarding the request for a patent claim construction pursuant to Local Patent Rule 4.5(a).
This Court has jurisdiction over this action pursuant to 28 U.S.C. §§ 1331 and 1338(a).
Venue is proper under 28 U.S.C. §§ 1391(b) and 1400(b). This Court held a Markman hearing
on May 15, 2014 regarding patent claims in Plaintiff’s United States Patent Nos. 6,281,230 ( “the
’230 Patent”), 6,555,554 ( “the ’554 Patent”), 7,465,800 ( “the ’800 Patent”), 7,977,357 ( “the
’357 Patent”), 8,193,219 (“the ’219 Patent”), and 8,431,598 (“the ’598 Patent”). After carefully
considering the parties’ written and oral arguments regarding five claim terms in dispute

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covering the six patents listed above, this Court has construed several claim terms, as discussed
below.
FACTUAL AND PROCEDURAL BACKGROUND 1
The drug at issue in this case is called lenalidomide. Lenalidomide is a chemical that
decreases the concentration of tumor necrosis factor (“TNFa”) in cells. Elevated TNFa
concentrations have been linked to various malignant diseases. As a result, lenalidomide has
been found to be an effective treatment to these diseases.
Plaintiff markets lenalidomide under the brand name Revlimid®. Revlimid® is approved
by the United States Food and Drug Administration (“FDA”) to treat multiple myeloma, mantle
cell lymphoma, and myelodysplastic syndrome. 2 The patents at issue cover the pharmaceutical
compositions containing lenalidomide, the medical uses of lenalidomide, and crystal forms of
lenalidomide.
Defendants are generic pharmaceutical makers. Defendants filed an Abbreviated New
Drug Application (“ANDA”) with the FDA seeking approval to market a generic version of
Revlimid®.
On October 8, 2010, Plaintiff filed a Complaint against Natco claiming that the generic
version of Revlimid® infringed on Plaintiff’s patents. On January 7, 2011, Plaintiff filed an
Amended Complaint adding Arrow as a defendant. On March 25, 2011, Plaintiff filed a Second
Amended Complaint adding Watson as a defendant.
On October 18, 2013, the parties filed a Joint Claim Construction and Prehearing
Statement for the patents at issue. A Markman hearing was held before this Court on May 15,
2014.
1

Unless otherwise noted, the facts are taken from the parties’ submissions.
Use of Revlimid® to treat mantle cell lymphoma is not currently relevant to this litigation because Defendants
have not sought FDA approval to market its generic product for this indication.
2

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LEGAL STANDARD
Markman Hearing and Claim Construction
Patent claim construction is a matter of law for the court.

Markman v. Westview

Instruments, Inc., 52 F.3d 967, 979 (Fed. Cir. 1995). When interpreting a claim, courts should
initially look to intrinsic evidence, namely “the patent claims, the specification and the
prosecution history if in evidence.” Bristol-Myers Squibb Co. v. Immunex, 86 F. Supp. 2d 447,
448 (D.N.J. 2000). “[I]ntrinsic evidence is the most significant source of the legally operative
meaning of disputed claim language.” Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582
(Fed. Cir. 1996). “The court should presume that the terms in the claim mean what they say,
and, unless otherwise compelled, give full effect to the ordinary and accustomed meaning of
claim terms.” Bristol-Myers Squibb Co., 86 F. Supp. 2d at 448. A person of ordinary skill in the
art “is deemed to read the claim term . . . in the context of the entire patent.” Phillips v. AWH
Corp., 415 F.3d 1303, 1313 (Fed. Cir. 2005); see Medrad, Inc. v. MRI Devices Corp., 401 F.3d
1313, 1319 (Fed. Cir. 2005) (“We cannot look at the ordinary meaning of the term . . . in a
vacuum. Rather, we must look at the ordinary meaning in the context of the written description
and the prosecution history.”) (citation omitted); see also Markman, 52 F.3d at 979.
If the intrinsic evidence alone will not resolve the ambiguity, the court may rely on
extrinsic evidence, which includes expert testimony, treatises, dictionaries and articles. BristolMyers Squibb Co., 86 F. Supp. 2d at 448-49. Extrinsic evidence may not be used to vary or
contradict the meaning established by the intrinsic evidence. Phillips, 415 F.3d at 1318-19,

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1324. “The construction that stays true to the claim language and most naturally aligns with the
patent’s description of the invention will be . . . the correct construction.” Id. at 1316.
A key aspect of claim construction is to assist the jury in understanding complicated
language and concepts. See Encap LLC v. Oldcastle Retail, Inc., No. 11-cv-808, 2012 WL
2339095, at *9 (E.D. Wis. June 19, 2012) (“Claim construction is not intended to allow for
needless substitution of more complicated language for terms easily understood by a lay jury.”);
see also C.R. Bard, Inc. v. United States Surgical Corp., 388 F.3d 858, 863 (Fed. Cir. 2004)
(“[M]erely rephrasing or paraphrasing the plain language of a claim by substituting synonyms
does not represent genuine claim construction.”); AFG Indus., Inc. v. Cardinal IG Co., Inc., 239
F.3d 1239, 1247 (Fed. Cir. 2001) (“It is critical for trial courts to set forth an express
construction of the material claim terms in dispute, in part because the claim construction
becomes the basis of the jury instructions, should the case go to trial. It is also the necessary
foundation of meaningful appellate review.”) (internal citation omitted).
DISCUSSION
1.

“[S]aid compound has the R-configuration” and “said compound has the Sconfiguration”
Plaintiff and Defendants disagree on the construction of “said compound has the R-

configuration” as used in claims 15 and 24 of the ’230 Patent and claims 2 and 14 of the ’554
Patent.

Similarly, the parties dispute the construction of “said compound has the S-

configuration” as used in claims 16 and 25 of the ’230 Patent and claims 3 and 15 of the ’554
Patent. Plaintiff contends that “said compound has the R-configuration” means “said compound
has the R-isomer” and that “said compound has the S-configuration” means “said compound has
the S-isomer.”

Defendants define “said compound has the R-configuration” as “the

stereochemical configuration of the compound is all or substantially all the R-isomer, thus
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excluding a compound that is a racemic mixture” and they define “said compound has the Sconfiguration” as “the stereochemical configuration of the compound is all or substantially all
the S-isomer, thus excluding a compound that is a racemic mixture.”
The references to “R-configuration” and “S-configuration” relate to different
“enantiomers” of the lenalidomide molecule. (Defs. Op. Br. 26.) “Enantiomers are different
versions of the molecule that have the same chemical formula and structural formula, but differ
in the three-dimensional orientation of their atoms in space.” (Id.) When a compound is made
up of both “R” and “S” isomers, it is said to be a “racemic mixture,” or a “racemate.” (See id. at
27.)
This Court finds that “said compound has the R-configuration” means “the
stereochemical configuration of the compound is all or substantially all the R-isomer, thus
excluding a compound that is a racemic mixture” and “said compound has the S-configuration”
to mean “the stereochemical configuration of the compound is all or substantially all the Sisomer, thus excluding a compound that is a racemic mixture.”

These constructions are

supported by the intrinsic evidence. The claim language at issue expressly requires that the
compound being administered have the “R-configuration” or the “S-configuration.” A person of
ordinary skill in the art (“POSA”) would focus on the particular enantiomer and not the racemic
mixture. See e.g., Ortho-McNeil Pharm., Inc. v. Mylan Labs., Inc., 348 F. Supp. 2d 713, 724
(N.D.W. Va. 2004) (noting that “chemists skilled in the art regard levorotatory enantiomers as
distinct from racemic compounds or the dextrorotatory enantiomer”). This is particularly clear
when contrasting the disputed terms with broader claims which reference the compound without
regard to the stereochemical configuration. See U.S. Patent No. ’230, at col. 27:30-55, 28:23-47.
In such instances, a POSA would understand these claims to cover racemic mixtures, which is

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within the scope of the invention, per the specification. See id. at col. 8:1-8 (stating “[t]he
compounds of the present invention possess a center of chirality and can exist as optical isomers.
Both the racemates of these isomers and the individual isomers themselves, as well as
diastereomers when there are two chiral centers, are within the scope of the present invention”).
Additionally, courts interpreting claims directed to single enantiomers have consistently
excluded the racemic mixture. See Teva Neuroscience, Inc. v. Watson Labs., Inc., 10-5078,
2013 WL 1595585, at *7 (D.N.J. Apr. 12, 2013) (construing “R(+)-N-propargyl-l aminoindan”
to mean, in relevant part, “at least substantially pure and may include small amounts of the other
enantiomer”); Ortho-McNeil Pharm., Inc., 348 F. Supp. 2d at 724 (noting that “each type of
compound has its own unique nomenclature. ‘S(-)’ clearly designates the levorotatory
enantiomer in this case. Had the inventor meant to designate the racemic compound, he would
have used the designation ‘(±)’ or “RS”). Consistent with this approach, this Court construes
“said compound has the R-configuration” as “the stereochemical configuration of the compound
is all or substantially all the R-isomer, thus excluding a compound that is a racemic mixture” and
“said compound has the S-configuration” as “the stereochemical configuration of the compound
is all or substantially all the S-isomer, thus excluding a compound that is a racemic mixture.”
2.

“Hemihydrate”
The parties disagree on the construction of “hemihydrate” as used in claims 1 through 14

of the ’800 Patent. Plaintiff defines “hemihydrate” as “a hydrate containing approximately half a
mole of water to one mole of the compound forming the hydrate.” Defendants contend that
“hemihydrate” means “a solid crystalline form of lenalidomide containing one water molecule
for every two molecules of 3-(4-amino-1-oxo-1,3 dihydro-insoindol-2-yl)-piperidine-2,6-dione,
formally associated with one another within the unit cell in the solid crystalline structure, and

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which crystal form is specifically identified in the ’800 patent as the Form B polymorphic form,
and demonstrated TGA, Karl Fischer analysis, powder X-ray diffraction patterns, IR spectra,
and/or DSC analysis, as distinguishable from other polymorphs, such as the anhydrous form.”
This Court finds that “hemihydrate” means “a hydrate containing approximately half a
mole of water to one mole of the compound forming the hydrate.”

This construction is

supported by the intrinsic evidence. The claim language does not limit the molar ratio to be an
exact 1:2 ratio of water to lenalidomide. See e.g., U.S. Patent No. ’800, at col. 22:40-43 (stating
in claim 10 that “[t]he hemihydrate of claim 1 having between approximately 0.46 and
approximately 0.59 moles of water per mole of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)piperidine-2,6-dione”); see also id. at col. 6:67-7:5, Figs 9, 37, 38, 39. Moreover, a hemihydrate
cannot mean an exact 1:2 ratio while simultaneously limiting the claims to Form B because the
specification explicitly describes an example of a Form B polymorph as a hemihydrate that
contains a ratio of water to lenalidomide that is not an exact 1:2 ratio. U.S. Patent No. 800, at
col. 6:64-7:6, 22:40-43, figs 9, 37-39 (describing hemihydrates containing anywhere from 0.46
to 0.59 molecules of water per molecule of lenalidomide). As the Federal Circuit has articulated,
“although the specification often describes very specific embodiments of the invention, we have
repeatedly warned against confining the claims to those embodiments.” Phillips, 415 F.3d at
1323. Reading in the specific embodiments of an exact 1:2 ratio would thus be improper here.
Accordingly, this Court finds that “hemihydrate” means “a hydrate containing approximately
half a mole of water to one mole of the compound forming the hydrate.”
3. “Form A”
The parties dispute the construction of “Form A” as used in the following instances: (1)
the ’357 Patent in claims 1 through 14; and (2) the ’598 Patent in claims 1 through 4. Plaintiff

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defines “Form A” as “a polymorphic form of 3-(4-amino-1-oxo-1,3 dihydro-insoindol-2-yl)piperidine-2,6-dione that can be distinguished from other forms.” Defendants contend that
“Form A” means “the lenalidomide crystal form described in the specification as Form A, having
all of the characteristics assigned to Form A in the specification.”
This Court finds that “Form A” means “the lenalidomide crystal form described in the
specification as Form A, having all of the characteristics assigned to Form A in the
specification.”

This construction is supported by the intrinsic evidence.

The ’357 Patent

specification expressly defines Form A based on observed attributes that are distinguishable from
the other disclosed forms—B, C, D, E, F, G, and H. U.S. Patent No. ’357, at col 6:13-10:30.
Examples of such characteristics unique to Form A include a specific X-ray powder diffraction
pattern, specific IR and Raman spectra, specific thermal characteristics, and representative
moisture sorption and desorption data. Id. at col. 6:13-54, Figs. 1-5. Notably, the other “Forms”
are also defined in the specification based on their observed attributes. Id. at col. 6:55-10:30
(defining Forms B through H). Based on the specification, a POSA would understand Form A to
mean a particular polymorph with these distinguishing characteristics.
Moreover, construing “Form A” to have all of these characteristics clarifies the scope of
the term as read in context of the claim language. See Smith v. Snow, 294 U.S. 1, 14 (1935)
(noting that “if the claim were fairly susceptible to two constructions, that should be adopted
which will secure to the patentee his actual invention”); Modine Mfg. Co. v. United States Int’l
Trade Comm’n, 75 F.3d 1545, 1556 (Fed. Cir. 1996) (“When claims are amenable to more than
one construction, they should when reasonably possible be interpreted so as to preserve their
validity.”). To ignore the specific attributes of Form A as defined in the specification would
render such language meaningless and give no meaning to the term “Form A.” Accordingly, this

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Court finds that “Form A” means “the lenalidomide crystal form describe in the specification as
Form A, having all of the characteristics assigned to Form A in the specification.”
4. Phrases Including “Form A” Terms
The parties dispute the construction of “Form A” as it appears in the following instances:
(1) “unsolvated crystalline Form A of 3-(4-amino-1-oxo-1,3 dihydro-insoindol-2-yl)-piperidine2,6-dione, which has a differential scanning calorimetry thermogram having an endotherm at
approximately 270°C” as it appears in claim 1 of the ’357 Patent; and (2) “unsolvated crystalline
Form A of 3-(4-amino-1-oxo-1,3 dihydro-insoindol-2-yl)-piperidine-2,6-dione having a
differential scanning calorimetry thermogram having an endotherm at approximately 270°C” as
it appears in claim 1 of the ’598 Patent. Defendants propose that the disputed term means “the
lenalidomide crystal form described in the specification as Form A, having all of the
characteristics assigned to Form A in the specification.” Plaintiff contends that no construction
is necessary for these terms.
For all of the reasons articulated above, this Court finds that “Form A” as it appears in the
disputed terms means “the lenalidomide crystal form described in the specification as Form A,
having all of the characteristics assigned to Form A in the specification.”
5. “Unsolvated Crystalline [lenalidomide]” Terms
The parties dispute the construction of the following terms: (1) “unsolvated crystalline 3(4-amino-1-oxo-1,3 dihydro-insoindol-2-yl)-piperidine-2,6-dione having an X-ray powder
diffraction pattern comprising peaks at approximately 8, 14.5, 16, 17.5, 20.5, 24, and 26 degrees
2θ” as it appears in claim 1 of the ’219 Patent; (2) “an unsolvated crystalline form of 3-(4-amino1-oxo-1,3

dihydro-insoindol-2-yl)-piperidine-2,6-dione

having

a

differential

scanning

calorimetry thermogram endotherm at approximately 270°C and an X-Ray powder diffraction

9

pattern comprising peaks at approximately 8, 14.5, and 16 degrees 2θ and a thermogravimetric
analysis curve of indicative of an unsolvated material” as it appears in claim 5 of the ’598 Patent;
(3) “an unsolvated crystalline form of 3-(4-amino-1-oxo-1,3 dihydro-insoindol-2-yl)-piperidine2,6-dione having an X-Ray powder diffraction pattern comprising peaks at approximately 8,
14.5, 16, 17.5, 20.5, 24, and 26 degrees 2θ” as it appears in claim 10 of the ’598 Patent; and (4)
“an unsolvated crystalline form of 3-(4-amino-1-oxo-1,3 dihydro-insoindol-2-yl)-piperidine-2,6dione having a differential scanning calorimetry thermogram endotherm at approximately
270°C” as it appears in claims 1 and 17 of the ’598 Patent. Defendants propose the following
construction for all the disputed terms: “the lenalidomide crystal form described in the
specification as Form A, having all of the characteristics assigned to Form A in the
specification.” Plaintiff contends that the disputed terms do not require construction.
This Court finds that the disputed terms do not require construction. Unlike the instances
that specifically reference “Form A,” the disputed terms here do not. Phrases that do not use the
term “Form A” should not be construed to have the same meaning as those including the term
“Form A.” No viable or cogent arguments have been presented to the contrary. Accordingly, this
Court finds that the disputed terms do not require construction.
CONCLUSION
For the reasons stated above, this Court orders that the disputed claims in the ’230 Patent,
the ’554 Patent, the ’800 Patent, the ’357 Patent, the ’598 Patent and the ’219 Patent be
construed as set forth in this Opinion. A summary of this Court’s construction of the disputed
claims is provided in the corresponding Order.
s/ Susan D. Wigenton
Susan D. Wigenton, U.S.D.J.
cc: Madeline Cox Arleo, U.S.M.J.
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