BRISTOL-MYERS SQUIBB COMPANY v. APOTEX, INC. et al

Filing 142

MEMORANDUM OPINION AND ORDER regarding construction of the disputed claims of the '746 Patent, the '875 Patent, the '856 Patent and the '867 Patent. Signed by Judge Mary L. Cooper on 3/28/2013. (gxh)

NOT FOR PUBLICATION
UNITED STATES DISTRICT COURT
DISTRICT OF NEW JERSEY
BRISTOL-MYERS SQUIBB CO.,
Plaintiff,
v.
APOTEX, INC., et al.,
Defendants.

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CIVIL ACTION NO. 10-5810 (MLC)
MEMORANDUM OPINION & ORDER

COOPER, District Judge
Plaintiff, Bristol-Myers Squibb Co. (“BMS”), commenced this
action against defendants, Apotex, Inc. and Apotex, Corp.
(collectively, “Apotex”), alleging, inter alia, that Apotex had
filed an Abbreviated New Drug Application (“ANDA”) with the
United States Food and Drug Administration (“FDA”) that would
infringe four of its patents in violation of 35 U.S.C. §
271(e)(2).

(See dkt. entry no. 1, Compl.)

The parties dispute the proper construction of claims
throughout four of BMS’s patents: United States Patent Nos.
6,596,746 (“the ‘746 Patent”), 7,125,875 (“the ‘875 Patent”),
7,153,856 (“the ‘856 Patent”), and 7,491,725 (“the ‘725
Patent”).
claims.

The parties seek the Court’s construction of these
The Court has considered the papers submitted by the

parties, and heard oral argument on September 10, 2012, and
October 2, 2012, and thereby conducted its Markman hearing.

See

Markman v. Westview Instruments, Inc., 52 F.3d 967 (Fed.Cir.
1995), aff’d, 517 U.S. 370 (1996).

Accordingly, the Court

hereby issues the following findings of fact and conclusions of
law with respect to its construction of the disputed claims of
the ‘746 Patent, the ‘875 Patent, the ‘856 Patent, and the ‘867
Patent.
BACKGROUND AND FACTUAL FINDINGS
I.

Background
A.

ANDA Process

This action arises under the Drug Price Competition and
Patent Term Restoration Act of 1984, Pub.L. No. 98-417, 98 Stat.
1585 (1984) (codified at 21 U.S.C. §§ 355, 360cc; 35 U.S.C. §§
156, 271, 282), as amended by the Medicare Prescription Drug,
Improvement, and Modernization Act of 2003, Pub.L. No. 108-173,
117 Stat. 2066 (2003) (collectively, the “Hatch-Waxman Act”). 1
Sale of a new drug is prohibited without approval from the FDA.
21 U.S.C. § 355(a).

To obtain approval, a pioneering

manufacturer must file a new drug application (“NDA”) containing
clinical studies of the drug’s safety and efficacy.
355(b)(1).

21 U.S.C. §

The manufacturer must also identify all patents that

1

The Court is guided by the format used by the United
States Court of Appeals for the Federal Circuit in citing the
Hatch-Waxman Act. See, e.g., Janssen Pharmaceutica, N.V. v.
Apotex, Inc., 540 F.3d 1353, 1355 (Fed.Cir. 2008).
2

claim the drug or a method of use.

21 U.S.C. § 355(b)(1)(G).

The FDA publishes a list of drugs and the applicable patents in
its Approved Drug Products With Therapeutic Equivalence
Evaluations, known as the “Orange Book.”

Novo Nordisk A/S v.

Caraco Pharm. Labs., Ltd., 601 F.3d 1359, 1361 (Fed.Cir. 2010).
A manufacturer seeking to market a generic copy of these
listed drugs may submit an ANDA.

21 U.S.C. § 355(j).

This

abbreviated process streamlines FDA approval by allowing the
generic manufacturer to rely on the safety and efficacy studies
of a drug already listed in the Orange Book upon a showing of
bioequivalence.

21 U.S.C. § 355(j)(2)(A)(iv).

As part of the

ANDA process, a generic manufacturer must certify one of four
statements concerning the applicable listed drug: (I) no such
patent information has been submitted to the FDA; (II) the
patent has expired; (III) the patent is set to expire on a
certain date; or (IV) the patent is invalid or will not be
infringed by the manufacture, use, or sale of the generic drug
(“Paragraph IV”).

21 U.S.C. § 355(j)(2)(A)(vii).

The Hatch-Waxman Act facilitates early resolution of
disputes between pioneering and generic manufacturers by
treating a Paragraph IV certification as an act of patent
infringement.

35 U.S.C. § 271(e)(2).

A generic manufacturer

filing a Paragraph IV certification must provide the patentee
3

and the NDA holder with a detailed basis for its belief that the
patent is invalid or not infringed.
355(j)(2)(B)(i).

21 U.S.C. §

The patentee has forty-five days to sue the

generic manufacturer for infringement.
355(j)(5)(B)(iii).

21 U.S.C. §

If the patentee does not sue, then the FDA

may approve the ANDA.

If the patentee sues, then the FDA may

not approve the ANDA until expiration of the patent, resolution
of the suit, or thirty months after the patentee’s receipt of
notice, whichever is earlier.

21 U.S.C. § 355(j)(5)(B)(iii).

“If the court determines that the patent is not invalid and that
infringement would occur, and that therefore the ANDA
applicant’s paragraph IV certification is incorrect, the patent
owner is entitled to an order that FDA approval of the ANDA
containing the paragraph IV certification not be effective until
the patent expires.”

Bayer AG v. Elan Pharm. Research Corp.,

212 F.3d 1241, 1245 (Fed.Cir. 2000) (internal citation omitted).
B.

The Parties

BMS is a Delaware corporation with its principal place of
business in New York and multiple research and development sites
in New Jersey.

(See Compl. at ¶ 2.)

BMS is the assignee of the

‘746 Patent, the ‘875 Patent, the ‘856 Patent, and the ‘725
Patent.

(See id. at ¶¶ 16-23.)

4

BMS markets the drug dasatinib under the trade name of
Sprycel© for the treatment of cancer, including chronic myeloid
leukemia (“CML”); the drug and methods of use are covered by the
suite of four patents.

(See dkt. entry no. 62, Pl. Opening

Claim Construction Br. at 1 (“Pl. Opening Br.”).)
Patent claims, inter alia, the compound dasatinib.

The ‘746
(See id.)

The ‘875 Patent claims methods of using dasatinib to treat
cancer, including treatment of CML.

(See id.)

The ‘856 Patent

claims methods of using dasatinib to treat cancer via oral
administration.

(See id.)

The ‘725 Patent claims, inter alia,

a crystalline monohydrate form of dasatinib.

(See id.)

BMS

holds a NDA approved by the FDA for dasatinib tablets, NDA No.
21-986.

(See Compl. at 24.)

Apotex, Inc. is incorporated in Canada, and Apotex Corp. is
a Delaware corporation with a place of business in Florida.
(See Compl. at ¶¶ 3-4.)

Apotex Corp. serves as the marketing

and sales affiliate in the United States for Apotex, Inc.
id. at ¶ 5.)

(See

Pursuant to Section 505 of the Federal Food, Drug,

and Cosmetic Act, 21 U.S.C. § 355(a), Apotex filed an ANDA for
dasatinib tablets with the FDA.

(See id. at ¶ 26.)

Apotex

wishes to manufacture, use, import, and sell a generic dasatinib
tablet, which would have the same indications as BMS’s Sprycel©
product.

(See id. at ¶¶ 26-31.)

BMS alleges that Apotex’s
5

generic dasatinib tablet infringes the ‘746 Patent, the ‘875
Patent, the ‘856 Patent, and the ‘725 Patent.
31.)

(See id. at ¶

Apotex sent written notice to BMS of its ANDA filing

declaring, inter alia, noninfringement and invalidity as to the
‘746 Patent, the ‘875 Patent, the ‘856 Patent, and the ‘725
Patent.

(See id. at ¶ 28.)

BMS asserts claims 6, 7, 18, 27-30,

32, 33, 42-44, and 46-48 of the ‘746 Patent; claims 1-3, 5, 7,
9-12, 14, and 27 of the ‘875 Patent; and claim 1 of the ‘856
Patent.

(See Pl. Opening Br. at 1.)

asserts claims 1-16.

From the ‘725 Patent, BMS

(See id. at 2.)

The asserted claims overlap in some combinations of the
various terms in dispute.

For instance, claim 6 of the ‘746

Patent contains the terms “salt”, “compound”, “selected from a
group consisting of” and a chemical name, whereas claim 43 of
the ‘746 Patent employs the terms “salt”, “compound” and a
chemical structure.

(See ‘746 Patent at col. 276, lines 51-53;

col. 302, lines 9-19.)

Where advisable, the Court has addressed

the terms together, but similar to how the parties addressed the
terms in the papers, some terms were also construed
individually.

(See, e.g., Pl. Opening Br. at 5-7; dkt. entry

no. 63, Defs. Opening Claim Construction Br. at 5-8 (“Defs.
Opening Br.”).)

6

II.

The Patents
A.

The ‘746 Patent

The ‘746 Patent discloses “[n]ovel cyclic compounds and
salts thereof, pharmaceutical compositions containing such
compounds, and methods of using such compounds in the treatment
of protein tyrosine kinase-associated disorders such as
immunologic and oncologic disorders.”

(‘746 Patent, Abstract.)

One of the compounds covered by the patents at issue is
dasatinib; the drug works as a treatment for CML, which is tied
to the “Philadelphia Chromosome.”

(See dkt. entry no. 86, Tr.

of Markman Hr’g on Sept. 10, 2012 at 7 (“9-10-12 Transcript”).)
The Philadelphia Chromosome is a mutated gene, created as a
result of a fusion of chromosome 9 and chromosome 22.

(See id.)

This gene causes an overproduction of tyrosine kinase, an
enzyme. (See id.)

Tyrosine kinase is a key element in the

regulation of cell signaling, including cell proliferation and
cell differentiation.

(‘746 Patent at col. 1, lines 19-21.)

Enhanced activity of the enzyme causes the proliferation of
malignant and nonmalignant cells, which can lead to CML.

(See

id. at col. 1, lines 35-44; see also 9-10-12 Transcript at 7.)
Dasatinib is an inhibitor of tyrosine kinase.
Transcript at 7.)

7

(See 9-10-12

The ‘746 Patent is composed of 49 claims, of which claims
1, 3, 4, 6, 7, and 43 are independent.
269–302.)

(‘746 Patent at cols.

Phrases found in claims 6, 7, 43, 44, and 47 of the

‘746 Patent require construction.

Claim 6 describes

“[a] compound or salt thereof selected from the group consisting
of . . . ‘N-(2-Chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)1-piperazinyl]-2-methyl-4-pyrimidinyl]amino-5thiazolecarboxamide.” 2
292, lines 46-48.)

(Id. at col. 276, lines 51-53 and col.

Claims 7, 44, and 47 all contain similar

language requiring construction by the Court, as exemplified by
the specific phrases in Claim 7:
A method for the treatment of a protein tyrosine
kinase-associated disorder, comprising the step of
administering to a subject in need thereof an amount
effective therefor of at least one compound of formula
III or a salt thereof:

2

Claim 6 includes several pages of different chemical
names, but the parties have both focused on this particularly
identified chemical. (See, e.g., Pl. Opening Br. at 7-8; see
also Defs. Opening Br. at 7-11.)
8

(Id. at col. 297, lines 38-50 (emphasis added); see id. at col.
302, lines 20-22, 28-31.)

Claim 43 requires construction as

well: “The compound

including salts thereof.” (Id. at col. 302, lines 9-19.)
B.

The ‘856 Patent

BMS is the assignee of the ‘856 Patent, which discloses
“[n]ovel cyclic compounds and salts thereof, pharmaceutical
compositions containing such compounds, and methods of using
such compounds in the treatment of protein tyrosine kinaseassociated disorders such as immunologic and oncologic
disorders.”

(‘856 Patent, Abstract.)

The ‘856 Patent issued

from a continuation application of the ‘746 Patent.
Opening Br. at 1.)

(See Pl.

The patent claims methods of using dasatinib

to treat cancer via oral administration.

(See id.)

The parties request construction of phrases in the
asserted claim 1: “A method for treatment of cancer, comprising

9

the step of administering orally to a subject in need thereof an
amount effective therefor of the compound

or salts thereof.”
(‘856 Patent at col. 278, lines 53-67 (emphasis added); see Pl.
Opening Br. at 9-15; see also Defs. Opening Br. at 8-14.)
C.

The ‘875 Patent

BMS is the assignee of the ‘875 Patent, which was filed on
March 24, 2003, and issued on October 24, 2006.

The ‘875 Patent

discloses “[n]ovel cyclic compounds and salts thereof,
pharmaceutical compositions containing such compounds, and
methods of using such compounds in the treatment of protein
tyrosine kinase-associated disorders such as immunologic and
oncologic disorders.”

(‘875 Patent, Abstract.)

The parties seek construction of phrases that are repeated
in claims 1, 2, 3, 11, and 27.

The language in claim 1 serves

as an example: “A method for the treatment of a cancer
comprising administering to a subject in need thereof an

10

effective amount of the compound of formula III or a salt
thereof:

.”
(emphasis added).)

(Id. at col. 276, lines 51-63

The phrase “administering to” appears in

claims 1, 2, 3, 11, and 27.

(See id. at col. 276, line 54; id.

at col. 277, lines 11, 35; id. at col. 278, line 42.)
phrase “administered . . .

to” appears in claim 5.

The
(See id. at

col. 277, line 66.)
A phrase that is repeated in claims 9, 10, and 27, and a
similar phrase in 12 and 16, require construction.

Claim 9

provides one example: “The method of claim 1 wherein the cancer
is resistant to treatment by STI-571.”

(Id. at col. 278, lines

36-37 (emphasis added); see id. at col. 278, lines 38-39.)
Claim 12 provides the other: “The method of claim 11, wherein
the chronic myelogenous leukemia (CML) is resistant to STI-571.”
(Id. at col. 278, lines 60-61 (emphasis added).)
D.

The ‘725 Patent

BMS is the assignee of the ‘725 Patent, which was filed on
July 29, 2005, and issued on February 17, 2009.

The ‘725 Patent

discloses “processes for preparing compounds having the formula

11

and crystalline forms thereof,
wherein Ar is aryl or heteroaryl, L is an optional alkylene
linker, and R2, R3, R4, and R5, are defined as in the
specification herein, which compounds are useful as kinase
inhibitors, in particular, inhibitors of protein tyrosine kinase
and p38 kinase.”

(‘725 Patent, Abstract.)

The patent claims,

inter alia, a crystalline monohydrate form of dasatinib, and it
is not tied closely with the other three patents at issue in
this suit.

(See Pl. Opening Br. at 1.)

The patented invention

represents an improvement in making 2-aminothiazole-5carboxamides over previously disclosed processes.
Patent at col. 3, lines 1-10.)

(See ‘725

The prior art disclosed methods

that had “drawbacks with respect to the production of side
products, the use of expensive coupling reagents, less than
desirable yields, and the need for multiple reaction steps to
achieve the 2-aminothiazole-5-carboxamide compounds.”
col. 3, lines 6-10.)

12

(Id. at

From claims 1, 3, and 12, the parties request construction
of the phrase “crystalline monohydrate of the compound of
formula (IV)

.”
61.)

(Id. at col. 48, lines 48-

The parties also request construction of the phrase “which

is characterized by an x-ray powder diffraction pattern
substantially in accordance with that shown in FIG. 1,” found in
claim 1.

(Id. at col. 48, lines 62-63.)

Claim 2 requires

construction of the first part of the claim: “The compound of
claim 1”; the Court will construe the rest of the claim
separately: “which is characterized by differential scanning
calorimetry thermogram and a thermogravimetric analysis
substantially in accordance with that shown in FIG. 2.”

(Id. at

col. 48, lines 64-66.)
The parties request construction for the similar phrases of
“[t]he compound of claim 1,” “[t]he compound of claim 3,” “[a]
process for preparing the compound of claim 3,” “[t]he compound
of claim 9,” and “[t]he compound of claim 12.”
Br. at 21; see also Defs. Opening Br. at 34-36.)

(See Pl. Opening

come from claims 2, 4-11, and 13-16.
13

These phrases

(See ‘725 Patent at col.

48, line 64; see also id. at col. 49, lines 20, 22, 32, 36, 39;
id. at col. 50, lines 1, 6, 9, 30, 33, 35, 37.)
From claim 3, the following phrase needs construction:
“which is characterized by an x-ray powder diffraction pattern
(CuKα λ=1.5418 Å at a temperature of about 23°C.) comprising four
or more 2θ values selected from the group consisting of
18.0±0.2, 18.4±0.2, 19.2±0.2, 19.6±0.2, 21.2±0.2, 24.5±0.2,
25.9±0.2, and 28.0±0.2.” 3

(Id. at col. 49, lines 14-18.)

From

Claim 5, the parties seek construction of
characterized by unit cell parameters approximately
equal to the following dimensions: Cell dimensions:
a(Å)=13.8632(7); b(Å)=9.3307(3); c(Å)=38.390(2);
Volume=4965.9(4) Å3
Space group Pbca
Molecules/unit cell 8
Density (calculated) (g/cm3) 1.354.
(Id. at col. 49, lines 23-32.)

Additionally, the parties

request construction of a phrase from claims 8, 15, and 16:
“wherein the compound is substantially pure.”
lines 39-40; id. at col. 50, lines 35-38.)

(Id. at col. 49,

From claim 9, two

phrases require construction: “being further characterized by a
differential scanning calorimetry having a broad peak between
3

A certificate of correction was filed on May 11, 2010 to
correct the typographical error that resulted in a gamma symbol
instead of lambda. (See dkt. entry no. 62-1, Decl. of Jerry
Atwood, Ex. M.) Accordingly, the text will be construed by the
Court as if it read “CuKα λ=1.5418 Å” instead of “CuKα γ=1.5418
Å.”
14

approximately 95° C. and 130° C.” and

“which corresponds to the

loss of one water of hydration on thermogravimetric analysis”.
(Id. at col. 50, lines 2-5.) 4
claim 12.

These two phrases are repeated in

(Id. at col. 50, lines 25-28.)

In claim 10, the phrase “which is further characterized by
a weight loss of 3.48% by thermogravimetric analysis between
50° C. and 175° C.” also requires construction.
50, lines 6-8.)

(Id. at col.

In claim 11, the phrase “wherein the

differential scanning calorimetry further has a peak at
approximately 287°C.” requires construction.

(Id. at col. 50,

lines 9-11.)
DISCUSSION AND CONCLUSIONS OF LAW
I.

Applicable Legal Standards
The Court must determine the scope and meaning of the

patent claims as a matter of law.

Markman, 52 F.3d at 979.

Claim terms “are generally given their ordinary and customary
meaning.”

Phillips v. AWH Corp., 415 F.3d 1303, 1312 (Fed.Cir.

2005) (quotation omitted).

The ordinary and customary meaning

of a claim term is the meaning a “person of ordinary skill in
the art in question” would give to such term on the effective
4

The typographical error of inserting “13° C.” instead of
“130° C.” and misspelling “thermogravimetric” as
“thermogravitmetric” has also been corrected through the same
certificate of correction. (See Decl. of Jerry Atwood, Ex. M.)
Accordingly, the Court will read the term as “thermogravimetric”
and the temperatures as “95°C. and 130°C.”
15

filing date of the patent application.

Id. at 1313.

Such a

person is deemed to interpret the claim term in the context of
the entire patent, including the specification and prosecution
history.

See id.

It is appropriate to deviate from the

“ordinary” meaning of a claim term when the intrinsic evidence,
including the specification and prosecution history, “reveal[s]
a special definition given to a claim term by the patentee that
differs from the meaning it would otherwise possess.”

Id. at

1316.
The specification is “always highly relevant to the claim
construction analysis” and is “the single best guide to the
meaning of a disputed term.”

Honeywell Int’l, Inc. v. ITT

Indus., Inc., 452 F.3d 1312, 1318 (Fed.Cir. 2006) (internal
quotation omitted).

The specification may contain an

intentional disclaimer or a disavowal of claim scope by the
inventor, in which case the inventor’s intention, as expressed
in the specification, is dispositive.
1316.

Phillips, 415 F.3d at

It is, however, improper to read a limitation from the

specification into the claims.

See Teleflex, Inc. v. Ficosa N.

Am. Corp., 299 F.3d 1313, 1326 (Fed.Cir. 2002).
The Court also considers the patent’s prosecution history.
Phillips, 415 F.3d at 1317.

The prosecution history provides

evidence of how the inventor understood the patent.
16

See id.

The prosecution history also demonstrates whether the inventor
limited the invention during the course of the patent
prosecution, thus narrowing the scope of the ultimately patented
product.

See id.

The prosecution history reflects the ongoing

negotiations between the inventor and the United States Patent
and Trademark Office (“PTO”), and thus is often less clear and
less useful than the specification.

See id.

The Court may in certain circumstances consider “extrinsic
evidence,” including “expert and inventor testimony,
dictionaries, and learned treatises.”

Id.

In general, such

evidence is less reliable than its intrinsic counterparts.
id. at 1318.

See

In some situations, the ordinary meaning of claim

language as understood by a person of skill in the art will be
readily apparent, and claim construction will then involve the
simple application of the widely accepted meanings of commonly
understood words.

See id. at 1314.

In such circumstances,

general purpose dictionaries may be helpful.

See id.

Nonetheless, “heavy reliance on the dictionary divorced from the
intrinsic evidence risks transforming the meaning of the claim
term to the artisan into the meaning of the term in the
abstract, out of its particular context, which is the
specification.”

Id. at 1321.

Also, expert evidence may be

useful for certain limited purposes, but unsupported assertions
17

by experts as to the definition of a claim term are not useful,
and the after-the-fact testimony of the inventor is accorded
little, if any, weight in the claim construction inquiry.

See

id.
If, after applying these principles, the Court concludes
that a claim term remains “insolubly ambiguous,” it must hold
that the claim limitation is indefinite.

Honeywell Int’l, Inc.

v. Int’l Trade Comm’n, 341 F.3d 1332, 1340-42 (Fed.Cir. 2003).
When that occurs, the Court must strike down all claims of which
the term is a part as indefinite and therefore invalid pursuant
to 35 U.S.C. § 112.

See id. at 1338-39; see also Aero Prods.

Int’l, Inc. v. Intex Recreation Corp., 466 F.3d 1000, 1015-16
(Fed.Cir. 2006).
II.

Legal Standards Applied Here
A.

Construction of the ‘746, ‘875, and ‘856 Patents
1.

“A compound or salt thereof selected from the
group consisting of”

Claim 6 specifies a “compound or salt thereof selected from
the group consisting of,” and it is directed to a compound or
salt selected from a list of compounds that includes dasatinib.
(‘746 Patent at col. 6, lines 18-35.)
BMS proposes that the disputed term be given its plain
meaning as understood by a person of ordinary skill in the art:

18

“a compound or its salt selected from the claimed list.”
Opening Br. at 5-7.)

(Pl.

BMS argues that “selected from the group

consisting of” constitutes a form of alternative expression
commonly known as a Markush group, which limits the claimed
“compound or salt thereof” to those compounds which are
specifically named in claim 6.

(Id. at 5 (citing Manual of

Patent Examining Procedure § 2173.05(h) (8th ed. 2001)).)

BMS

argues that Apotex incorrectly assumes that the Markush group
concerns the purity of the claimed invention, when the patent
instead discloses that claimed compositions may contain other
ingredients besides the listed compounds for other preservation,
delivery, or dilution purposes.

(See id. at 6-7.)

BMS would

further read “salt” as it is defined in the ‘746 Patent
specification: “acidic and/or basic salts formed with inorganic
and/or organic acid or bases.”

(Id. at 6.)

Apotex argues that the term “compound” should be construed
“to reflect the specification’s express lexicography statements,
so the term includes prodrugs, solvates, salts and stereoisomers
of any particularly listed compound or structure.”
Opening Br. at 5.)

(Defs.

Accordingly, Apotex would have all salts

included in the term “compound” as well: “the term ‘compound’
should conform to the specification’s clear statement that the
term encompasses ‘salts’; ‘prodrugs and solvates of the
19

compound[]’; and ‘stereoisomers of the ... compound[]’ or salt
thereof.”

(Id. at 5-6.)

Apotex would draw the definition for

“salt” from language included in the specification:
The term “salt(s)”, as employed herein, denotes acidic
and/or basic salts formed with inorganic and/or
organic acids and bases. Zwitterions (internal or
inner salts) are included within the term “salt(s)” as
used herein (and may be formed, for example, where the
R substituents comprise an acid moiety such as a
carboxyl group). Also included herein are quaternary
ammonium salts such as alkylammonium salts.
Pharmaceutically acceptable (i.e., non-toxic,
physiologically acceptable) salts are preferred,
although other salts are useful, for example, in
isolation or purification steps which may be employed
during preparation.
(Id. at 6 (quoting ‘746 patent at col. 6, lines 21-31).)
Finally, relying on the claim construction reasoning of Abbott
Labs. v. Baxter Pharm. Prods., Inc., 334 F.3d 1274, 1280-81
(Fed.Cir. 2003), Apotex contends that the Markush group language
“precludes mixtures of the listed compounds and other compounds
not part of the list, including impurities.”

(Defs. Opening Br.

at 7.)
The court in Abbott Labs. reasoned that a patentee’s use of
“a” in conjunction with a Markush grouping should be construed
to exclude mixtures, including a mixture of compounds within the
Markush group list itself.

Abbott Labs., 334 F.3d at 1281 (“‘a’

with ‘consisting of’ in this case indicates only one member of a
Markush group. . . .

If a patentee desires mixtures or
20

combinations of the members of the Markush group, the patentee
would need to add qualifying language while drafting the claim”
such as “and mixtures thereof” or “at least one member of the
group”).

Apotex submits that, based on this, the patentee’s

failure to include any qualifying language in the ‘746 Patent
requires the Court to construe the claim so that “[a]ny
substance that mixes two compounds on the list (whether or not
as an impurity), or mixes one compound on the list and one off
the list, is outside the scope of this claim language.”

(Defs.

Opening Br. at 8.)
BMS replies that the disjointed treatment Apotex gives the
language in claim 6 introduces unnecessary ambiguity to avoid
applying the plain meaning of the terms.

(See dkt. entry no.

66, Pl. Responsive Claim Construction Br. at 4 (“Pl. Responsive
Br.”).)

BMS further argues that the claim language at issue in

Abbott Labs. was directed at a “composition” in combination with
Markush group terms.

(See id. at 5.)

BMS argues that the case

cited by Apotex is distinguishable from the present claim
language because Abbott Labs. does not address whether use of
the phrase “consisting of” without “a” precludes impurities in a
preparation of the compound.

See Abbott Labs., 334 F.3d at

1276, 1281; see also Teva Pharm. USA Inc. v. Amgen, Inc., No.
09-5675, 2010 U.S. Dist. LEXIS 95288, at *20-21 (E.D.Pa. Sept.
21

10, 2010) (rejecting proposed construction that use of a Markush
group means that “there can be only one member of the Markush
group present in a product and, if there are more, then the
product is outside the scope of the patent”).

(See Pl.

Responsive Br. at 4-5.)
The Court has considered the patent claims and
specification, as well as the parties’ respective arguments.
The Court agrees with the patentee that the Markush group
language is here properly utilized to include any pharmaceutical
composition containing a compound listed in the claim.

The

definitions for “compound” and “salt” proposed by Apotex rely on
phrases pulled out of context from the specification that are
not properly applied to the claims in order to distort its
construction.

The Court construes the term “a compound or salt

thereof selected from the group consisting of” to conform with
the patentee’s requested definition, namely the plain meaning of
the term as understood by a person of ordinary skill in the art:
“[A] compound or its salt (‘salt’ meaning acidic and/or
basic salts formed with inorganic and/or organic acid and bases)
selected from the claimed list.”

22

2.

Chemical names identified in Claim 6 including
“’N-(2-Chloro-6-methylphenyl)-2-[[6-[4-(2hydroxyethyl)-1-piperazinyl]-2-methyl-4pyrimidinyl]amino-5-thiazolecarboxamide”

Claim 6 lists many chemical names, including a “’N-(2Chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]2-methyl-4-pyrimidinyl]amino-5-thiazolecarboxamide.”
Patent at col. 292, lines 46-48.)

(‘746

The chemical names form a

list of compounds that includes dasatinib.

(‘746 Patent at col.

6, lines 18-35.)
The patentee has proposed a construction of the term as
follows: “’N-(2-Chloro-6-methylphenyl)-2-[[6-[4-(2hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino-5thiazolecarboxamide represents the compound having the following
equivalent chemical structures:

.”

(See dkt. entry no. 51, Joint Claim

Construction & Prehearing Statement, Ex. 2 at 2 (“Joint
Statement”).)

BMS offers the opinion of an expert to confirm

23

that a person of ordinary skill in the art would interpret the
claim consistently with this plain reading and would further
recognize that the recited name is that of dasatinib.

(See Pl.

Responsive Br. at 6.)
Apotex counters that “[t]he chemical descriptors given in
claim 6 require the plain and ordinary meaning of such terms, to
be interpreted according to [International Union of Pure and
Applied Chemistry (“IUPAC”)] nomenclature guidelines.”
Statement at 2.)

(Joint

In support of its position, Apotex relies on

an expert, who claims that the IUPAC standard is the globally
recognized chemical nomenclature guide and that the name should
be construed under the IUPAC rules.
9.)

(See Defs. Opening Br. at

Apotex argues that ’N-(2-Chloro-6-methylphenyl)-2-[[6-[4-

(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino-5thiazolecarboxamide, when properly read under IUPAC’s naming
conventions, is not equivalent to dasatinib.

(See id.)

Apotex

specifically argues that, because two hydrogen atoms that would
be bound to two nitrogen atoms are not included on the chemical
structure pictured in Example 455 of the ‘746 Patent, dasatinib
is not an equivalent structure.

(See id. at 10.)

Apotex also

seeks to have the Court construe “’N-(2-Chloro-6-methylphenyl)2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4pyrimidinyl]amino-5-thiazolecarboxamide” in such a way as to
24

exclude the chemical dasatinib.

(See id. at 10-11.)

Apotex’s

expert provides that dasatinib is not included in the three
equivalent chemical structures that BMS would have the Court
construe as the meaning of this term.

(See id. at 9-10.)

BMS responded both in the papers and at oral argument that
it is a common understanding in the relevant art that chemical
illustrations representing real chemical structures employ some
shorthand, i.e., not every hydrogen atom in the chemical
compound must be depicted.

(See Pl. Opening Br. at 8; see also

9-10-12 Transcript at 77-78.)

BMS also points out that, when

Apotex’s expert was asked to draw out the structure associated
with ’N-(2-Chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1piperazinyl]-2-methyl-4-pyrimidinyl]amino-5-thiazolecarboxamide,
he drew the following depiction, and then identified the
chemical structure as that of dasatinib:

.

(See Pl. Responsive Br.

at 6-7.)

25

The Court has considered the parties’ respective arguments,
the patent claims and specification, and the extrinsic evidence
of expert opinions proffered by the parties.

The Court agrees

with the patentee that chemical structures sometimes are
depicted without every hydrogen atom drawn onto the structure;
such failure to show the hydrogen atoms on the chemical
structures depicted in the patent will not preclude the Court
from construing the term to include an equivalent structure with
the hydrogen atoms present.

Further, the Court rejects Apotex’s

proposal to exclude dasatinib from the scope of the named term
’N-(2-Chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1piperazinyl]-2-methyl-4-pyrimidinyl]amino-5-thiazolecarboxamide
because its own expert recognized that, when drawn, the term
represents a structure equivalent to and recognizable to a
person of ordinary skill in the art as being dasatinib.

The

Court thus construes the term “’N-(2-Chloro-6-methylphenyl)-2[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4pyrimidinyl]amino-5-thiazolecarboxamide” as follows:
the compound having the following equivalent chemical
structures

26

.
3.

“A method for the treatment of a protein tyrosine
kinase-associated disorder, comprising the step
of administering to a subject in need thereof an
amount effective therefor of at least one
compound of formula III or a salt thereof”

The terms “administering to” or “administering orally to”
and “subject in need thereof” appear in claims 7, 44, and 47 of
the ‘746 Patent, claim 1 of the ‘856 Patent, and claims 1, 2, 3,
11, and 27 of the ‘875 Patent.

These claims are directed to

treating a protein tyrosine kinase-associated disorder with at
least one compound of formula III or a salt thereof.
a.
“Administering to” or “administering
orally to”
BMS proposes that the term be construed with the help of an
extrinsic source, the Merriam-Webster’s Collegiate® Dictionary,
to mean “to mete out or dispense or to give remedially [the
compound in oral form, including but not limited to tablets,
capsules, granules or powders].”

27

(Pl. Opening Br. at 9.)

BMS

argues that, because the term was not explicitly defined in the
patent at issue, extrinsic evidence is available to “aid the
Court’s understanding of the patent.”

See Wright Med. Tech.,

Inc. v. Osteonics Corp., 122 F.3d 1440, 1443 (Fed.Cir. 1997).
(See Pl. Opening Br. at 9.)
BMS further argues that dictionaries are acceptable aids as
extrinsic evidence and that a similar dictionary definition of
“administering” has previously been accepted by courts
construing similar claim language.

See Phillips, 415 F.3d at

1318; see also Acorda Therapeutics, Inc. v. Apotex, Inc., No.
07-4937, 2011 WL 4074116, at *3, 26 (D.N.J. Sept. 6, 2011),
aff’d, 476 Fed.Appx. 746 (Fed.Cir. 2012) (construing a term in a
patent concerning a method of administering tizanidine
multiparticulates to patients with food as meaning “giving,
dosing, self-dosing or taking of the composition” with specific
plasma concentration results).

(See Pl. Opening Br. at 9.)

BMS

also argues that when the patent (which specifies various routes
of administration) is read as a whole, the term “administering
to” can be seen as distinct from any particularly specified
route of administration.

(See id. at 10.)

Apotex proposes a construction with two components: (1)
“administering” refers to an administration alone or in
combination, in a single dose or in divided doses, with or
28

without other agents, simultaneously or in succession; and (2)
two actors are required: the subject in need thereof and the
person responsible for giving the therapeutic agent.
Opening Br. at 15; see also Joint Statement at 3.)

(See Defs.
Apotex

relies on prosecution history and expert testimony in addition
to legal argument to bolster this construction.

(See Joint

Statement at 3.)
Apotex argues that this construction of “administering”
reflects the expansive teachings in the specification without
“introducing extraneous or other limiting elements into the
claim term.”

(Defs. Opening Br. at 15.)

Because the

specification teaches that such methods of “administering” can
occur, Apotex argues that the definition can and should include
those methods without placing limitations on the meaning beyond
the teachings of the patent.

(See id.)

Apotex argues that the

significance of “to” is made clear by examining the “claim
language and . . .

syntactic signs of its meaning.”

(Id.

(citing Eastman Kodak Co. v. Goodyear Tire & Rubber Co., 114
F.3d 1547, 1553 (Fed.Cir. 1997), abrogated on other grounds by
Cybor Corp. v. FAS Techs., Inc., 138 F.3d 1448 (Fed.Cir.
1998)).)

The term “administering to” or “administering orally

to” requires two actors: one who gives the agent and a subject
who is in need of treatment.

(See id. at 16.)
29

Apotex argues

that where a patentee has drafted a claim term implying there is
more than one actor, the patentee cannot then ask the Court to
penalize a single actor defendant who does not perform or
fulfill the claim in its entirety.

(See id. at 16-17.)

BMS responds that case law does not support Apotex’s
position: Eastman Kodak encourages courts to look to syntactic
context for signals of the meaning of “to”.
114 F.3d at 1553.

See Eastman Kodak,

(See Pl. Responsive Br. at 9.)

Here, the

only verb providing any such signal is “administering” and a
single actor is required for that.

(See id. at 9-10.)

“To” is

merely used to suggest a direction - toward the subject in need
thereof, who is not required to take any action to fulfill the
claim.

(See id. at 10.)

BMS also relies on Acorda

Therapeutics, Inc. for the proposition that such a term in a
claim could be fulfilled by a physician, pharmacist, or patient
alone.

See Acorda Therapeutics, Inc., 2011 WL 4074116 at *27.

Finally BMS argues that two actors are not required for
infringement even though animals are included in the potential
treatment population, thus identifying a population needing the
drug but unable to self-administer.
10.)

(See Pl. Responsive Br. at

BMS argues that this demonstrates the only actor targeted

by the claim is the one performing the administration of the
drug.

(See id.)

Apotex’s responsive brief argues that the
30

term, when read in context, requires two actors.

(See dkt.

entry no. 69, Defs. Responsive Claim Construction Br. at 13-14
(“Defs. Responsive Br.”).)
The Court has considered the parties’ respective arguments,
the patent claims and specification, and the extrinsic evidence
proffered by the parties.

The Court agrees with the patentee

that the term neither requires multiple actors nor specifies any
particular route of administration.

The Court thus construes

the terms “administering to” or “administering orally to” as
follows:
To mete out or dispense or to give remedially.

b. “a subject in need thereof”
BMS argues that this term should be given its plain meaning
as understood by a person of ordinary skill in the art.
Pl. Opening Br. at 11.)

BMS proposes that the term be construed

to mean “an animal, including a human, in need thereof”.
Statement at 4.)

(See

(Joint

For support, BMS relies on the specification,

which states “preferred subjects for treatment include animals,
most preferably mammalian species such as humans, and domestic
animals such as dogs, cats, and the like . . . .”
at col. 26, lines 53-57.)

(‘746 Patent

Quoting Phillips, BMS further argues

that the specification should serve as the “primary basis for
31

construing the claim” and as the “best source for understanding
a technical term.”

See Phillips, 415 F.3d at 1315.

Finally,

BMS argues that Apotex’s construction would impermissibly
broaden the meaning by extending its reach to “any living
organism”, which is in direct contravention of the more limited
sphere envisioned by the specification.

See ERBE Elektromedizin

GmbH v. Int’l Trade Comm’n, 566 F.3d 1028, 1034 (Fed.Cir. 2009)
(“We generally do not construe claim language to be inconsistent
with the clear language of the specification. Usually [the
language of the specification] is dispositive.”) (internal
citation omitted).

(See Pl. Opening Br. at 11.)

Apotex proposes that the term be construed to mean: “Any
living organism having a protein-kinase associated disorder
known to be susceptible to treatment with compounds of formula
III, as construed above, as diagnosed by a second party, likely
a physician or other clinician.”

(Joint Statement at 4.)

The

reasoning Apotex offers for this construction is that the
subject must be known to require such treatment before
administration of the disclosed compounds.
Br. at 13.)

(See Defs. Opening

In addition to the arguments advanced in their

briefs, Apotex explained at oral argument that the term requires
two actors because it includes “in need thereof”:
[T]his goes to a need for multiple actors. First of
all, you need the subject. And then you need somebody
32

to diagnose the disorder. I don’t think the patentee
specifically limited this patent to just those people
who are able to self-diagnose the disorder themselves,
but were meant to open it up to more than just those
people. And then, of course, if we’re talking about
non-human animals, then certainly a dog or cat would
not be able to diagnose themselves, and we would need
a second actor.
(9-10-12 Transcript at 179, lines 8-16.)

Apotex also relies on

the specifications of the ‘746, ‘875, and ‘856 Patents for the
proposition that a “subject in need thereof” is one suffering
from a protein tyrosine kinase-related disorder.
Opening Br. at 14.)

(See Defs.

Apotex argues that construction of the term

should be informed by the specifications, which describe the
field of the invention and the purpose of the method claimed as
being directed to the treatment of protein tyrosine kinase
associated disorders, such as immunologic and oncologic
disorders.

(See id.)

BMS responds to Apotex’s arguments regarding “in need
thereof” by distinguishing the two cases Apotex cited, neither
of which construed similar claim terms to require a second actor
for diagnosing purposes.

(See Pl. Responsive Br. at 10-11.)

Moreover, BMS argues that the only act being performed is
“administering” the compounds, and thus only one actor is
required.

(See id. at 11.)

33

Apotex, in its response, argues that BMS artificially
imports a limitation into the term “subject” that was not
intended from the specification.
11.)

(See Defs. Responsive Br. at

Apotex argues that merely expressing a preference for one

kind of subject (animals, most preferably mammalian) is not
sufficient to require the Court to limit the universe of
potential subjects to that expressed preference.

(See id.)

The

United States Court of Appeals for the Federal Circuit has
previously held that statements of preference in the
specification are not presumptively definitional.

See Liebel-

Flarsheim Co. v. Medrad, Inc., 358 F.3d 898, 913 (Fed.Cir. 2004)
(“[I]t is improper to read limitations from a preferred
embodiment described in the specification—even if it is the only
embodiment—into the claims absent a clear indication in the
intrinsic record that the patentee intended the claims to be so
limited.”) (internal citation omitted).

At oral argument,

however, counsel for Apotex argued that this should be read in
the broadest possible manner, unlimited by an expressed
preference in the specification.
MR. BENCHELL: So, what the specification tells
us is that the preferred definition for subjects, not
the—not subjects, not all subjects, but the preferred
definition is, “Subjects for treatment include
animals,” not just animals, but “include animals.”
So, to answer your earlier question, that would
include other living beings, whether that be animals,
whether that be your single cell amoebas, or whatever.
34

. . .
THE COURT: Do you know whether anything other
than an animal can get this—can develop this problem?
MR. BENCHELL: I do not know.
THE COURT: No. But I mean it seems to me that
if there’s no other organism that can develop this
problem, it’s a moot point.
MR. BENCHELL: Well, but you can also—I mean, you
know, to take it to the extreme, you can take the
cancer tumor, and that will continue to grow in a
petri dish. You can take those types of organs that
can continue to live outside the body.
(9-10-12 Transcript at 177-178.)
The Court has considered the parties’ respective arguments,
the patent claims, and specification.

The Court agrees with the

patentee that the intrinsic evidence does not limit the term by
requiring multiple actors nor must the field of potential
subjects be left open to the wide universe proposed by Apotex.
See Liebel-Flarsheim, 358 F.3d at 913.

Finally, the Court is

unpersuaded by Apotex’s argument to broaden the universe of
subjects to all living organisms when the intrinsic evidence
demonstrates that the drug was intended for those subjects with
the targeted disease -- animals, including humans.

The Court

thus construes the term “a subject in need thereof” as follows:
An animal, including a human, in need thereof.

35

4.

“Wherein the cancer is resistant to treatment by
STI-571”

The term appears in claims 9, 10, 12, and 27 of the ‘875
Patent, which are directed to methods for the treatment of
cancer “wherein the cancer is resistant to treatment by STI571.”

(See ‘875 Patent at col. 278, lines 35-40, 60-61; col.

282, line 15.)
BMS proposes that the term be given its ordinary and
customary meaning as understood by a person of ordinary skill in
the art.

(See Pl. Opening Br. at 17.)

BMS asks the Court to

construe the term to mean: “wherein the cancer [or chronic
myelogenous leukemia (CML)] exhibits resistance to treatment by
STI-571”.

(Joint Statement at 23.)

BMS argues that this

construction comports with the meaning of resistant as defined
in the Merriam-Webster’s Collegiate® Dictionary: “giving or
capable of resistance”.

(See Pl. Opening Br. at 17.)

BMS notes

that the ‘875 Patent discloses that the claimed compounds that
are the subject of the patent may be useful “in the treatment of
cancers that are sensitive to and resistant to chemotherapeutic
agents that target BCR-ABL and c-KIT, such as, for example,
Gleevec® (STI-571).”

(Id. at 17 (citing Jorgensen Ex. C, col.

28, ll. 26-28).)

36

Apotex argues that the term should be construed to require
both a subject in need of cancer treatment and a second actor
who diagnosed the cancer as being resistant to STI-571.
Defs. Opening Br. at 17.)

(See

Apotex argues that the ‘875 Patent

presents a specific objective for the use of the compounds that
creates a limitation on subsequent claims: “The compounds of the
present invention are also useful in the treatment of cancers
that are sensitive to and resistant to chemotherapeutic agents
that target BCR-ABL and c-KIT, such as, for example, Gleevec®
(STI-571).”
38).)

(See id. (citing ‘875 Patent at col. 28, lines 35-

Relying on this language in the specification, Apotex

argues that the resistance to STI-571 is a limitation
necessitating one actor be trained in the diagnosis and
treatment of cancer.

(See id. at 17-18.)

Apotex also cites two cases for support of this position.
(See id. at 17.)

In Jansen, the court determined that language

in the claim preamble established “the objective of the method,
and the body of the claim directs that the method be performed
on someone ‘in need.’

In both cases, the claims’ recitation of

a patient or a human ‘in need’ gives life and meaning to the
preambles’ statement of purpose.”

Jansen v. Rexall Sundown,

Inc., 342 F.3d 1329, 1333 (Fed.Cir. 2003).

In Schering, the

court was asked to construe the phrase “in need of such
37

treatment” after “the parties agreed that [the phrase] mean[t]
‘one or more therapeutic effects of the type identified in the
preamble are required or wanted.’”

Schering Corp. v. Glenmark

Pharms. Inc., No. 07-1334, 2008 WL 4307189, at *9 (D.N.J. Sept.
16, 2008) (finding the phrase “had intent written into it”, such
that the words “require” and “wanted” “intimate an intent to use
the drug for the purpose it was intended”).

Apotex also argues

that BMS’s proposed definition impermissibly broadens the scope
of the claim by changing the term from “is resistant to” to
“exhibits resistance”.

(See Defs. Responsive Br. at 14-15.)

These cases are distinguishable because the specification
does not include a purpose-driven declaration for the method
claimed as was the case in Jansen; rather the specification
notes that the drug can be useful for treatment where the
patient is resistant or sensitive to another drug.
342 F.3d at 1333.

See Jansen,

(See ‘875 Patent at col. 28, lines 35-38.)

Similarly, the parties in Schering agreed to a specific
definition that included the words “wanted” and “required”,
neither of which is present in or analogous to the phrase
“wherein the cancer is resistant to treatment by STI-571.”
Schering, 2008 WL 4307189, at *9.

See

Accordingly the Court rejects

Apotex’s argument that the phrase should be construed to require
two actors.

Moreover, the Court is unpersuaded by Apotex’s
38

arguments regarding the meaning of “is resistant to”.
Resistance, as BMS noted during oral argument, is not a
proposition of duality (entirely resistant or entirely
unresistant), but rather presents as a continuum along which
patients can exhibit degrees of resistance to treatment.
9-10-12 Transcript at 188-89.)

(See

Apotex’s argument creates a new

limitation by defining the term to only include those patients
who are completely resistant to STI-571, without any recognition
that such resistance may present in degrees of inefficacy in
that treatment.

(See Defs. Responsive Br. at 15; Pl. Opening

Br. at 17; 9-10-12 Transcript at 193-95.)
The Court has considered the parties’ respective
arguments, the patent claims, the specification and the
extrinsic evidence.

The Court agrees with the patentee that the

term does not require either multiple actors or complete
resistance to treatment by STI-571 as proposed by Apotex.

The

Court thus construes the term “wherein the cancer is resistant
to treatment by STI-571” as follows:
Wherein the cancer [or chronic myelogenous leukemia (CML)]
exhibits resistance to treatment by STI-571.

39

B.

Construction of the ‘725 Patent
1.

“Crystalline monohydrate of the compound of

formula (IV)

”

The term appears in claims 1, 3, and 12 of the ‘725 Patent,
which are directed to crystalline monohydrate compounds of
formula IV.

(See, e.g., ‘725 Patent at col. 48, lines 48-60.)

BMS proposes that the term be read to comport with its
plain meaning as understood by a person of ordinary skill in the
art, namely “the monohydrate of the compound of formula IV in a
crystalline form.”

(Joint Statement at 33.)

BMS finds support

for this argument in the specification, which provides an
example of the preparation of a crystalline monohydrate in
Example 8.

(See Pl. Opening Br. at 18.)

A monohydrate, BMS

argues, means “a compound containing one molecule of water.”
(See id. (citing The American Heritage® Dictionary 1137 (4th ed.
2000)).)
Apotex argues that “crystalline monohydrate” is only a
general term, given meaning by the intrinsic evidence of
specified results achieved upon analytical testing.
Opening Br. at 18.)

(See Defs.

Apotex would have the Court construe the
40

term to mean “[r]aw material produced by process conditions
presented in the specifications, with a particular arrangement

of the following compound:
in three dimensional space that has a certain degree of long
range order, with a 1:1 molar arrangement of water to compound
formally associated in a unit crystal cell lattice.”
Statement at 33.)

(Joint

Apotex argues that a “crystalline

monohydrate” is a general term encompassing multiple
polymorphous versions of crystal lattice frameworks.
Opening Br. at 19-20.)

(See Defs.

These different forms are identifiable

only through specific testing and observational means, and
therefore, Apotex argues, the claim should be limited to the
specific crystalline monohydrate described in the results
achieved through analytical testing.

(See id. at 19.)

Apotex also argues, based on a specification for an earlier
application, that the ‘725 Patent was not originally intended to
describe crystalline monohydrates.

(See id. at 20.)

Rather,

the “‘invention relates to process for preparing compounds’ of a
general formula, . . . [and the phrase] ‘and crystalline forms

41

thereof’ was a later addition to the ‘725 patent’s application,
which was originally filed as a patent application directed
towards only processes for preparing compounds.”

(Id.)

Apotex

places great weight on the precise methodologies for preparation
and testing that are mentioned in the ‘725 Patent, arguing:
the ‘725 patent is quite particular about the
methodologies that can be used to prepare the
“crystalline monohydrate of the compound of formula
(IV).” . . . It is clear to a person of ordinary skill
in the art reading the specification that the
particular processes that BMS originally sought to
patent were what prompted the monohydrate crystal
formulation.
(Id. at 20-21 (internal citations omitted).)

Apotex argues that

the invention must be “a stand-alone, raw material substance,
and not a mixture” for three reasons: (1) the only mixtures
mentioned in the ‘725 Patent are described in other dependent
claims and are made up of the drug with excipients in
pharmaceutical composition; (2) the specification states that
“[t]he present invention also provides using the compounds
obtained with the inventive process to further prepare
pharmaceutical compositions”; and (3) the results achieved
through analytical testing will only be “substantially” in
conformance with the figures listed in the claims if the
analytical tests are conducted on raw material samples.
id. at 21.)

(See

Apotex cites Abbott Labs. as support for limiting a

42

claim to the product when a specific crystal was the only
product capable of achieving the analytical test results set
forth in the specification and claims of the patent.

Abbott

Labs. v. Sandoz, Inc., 566 F.3d 1282 (Fed.Cir. 2009).
Apotex further argues under the prosecution history that
BMS should be limited to only those crystals that are produced
by the specification’s procedures.
22.)

(See Defs. Opening Br. at

During prosecution, the PTO Examiner rejected claims for

the crystalline monohydrate on the basis of prior art in the
field that would lead a person of ordinary skill in the art to
expect that compounds in the class would form hydrates and
solvates.

(See id.)

When BMS responded that the prior art did

not disclose a monohydrate of the compound of formula IV in a
crystalline form, the PTO in turn accepted the detailed
structural information and lack-of-expectation assertion as
entitling BMS to only “the crystalline forms that are adequately
described in the specification and [not granting BMS] a generic
crystalline claim.”

(See id. (citing Shannon Decl., Ex. G, ‘725

patent PH, 3/3/08 Office Action, at 4 (APO(Das)016420)).)
BMS responds that Phillips requires courts to construe
claim terms in light of the patent as a whole, including its
specification, and that the specification to be examined is the
one in the issued patent, not earlier versions.
43

(See Pl.

Responsive Br. at 13 n.3 (citing Sun Pharm. Indus., Ltd. v. Eli
Lilly & Co., 611 F. 3d 1381, 1388 (Fed.Cir. 2010) (quoting
Phillips, 415 F.3d at 1316)).)

Moreover, BMS notes that Apotex

points only to the testimony of its expert for support that the
term should be construed to mean a raw material that resulted
from the process conditions exemplified in Example 8.
at 13.)

(See id.

BMS highlights several concerns with the expert’s

opinion, notably his conclusion’s lack of foundation in the
intrinsic evidence, his failure to conduct experimentation to
produce the monohydrate through other procedures, and several
contradictory statements when his conclusion is compared to the
‘725 Patent as a whole.

(See id. at 14.)

BMS points out that

the same expert conceded the term “raw material” does not appear
in any of the claims of the ‘725 Patent, nor do the claims
expressly or implicitly limit the invention to the process
conditions.

(See id.)

With respect to Apotex’s reliance on

Abbott Labs., BMS responds that the Court of Appeals for the
Federal Circuit has already rejected that argument: “this court
expressly rejected the contention that if a patent describes
only a single embodiment, the claims of the patent must be
construed as being limited to that embodiment.”
566 F.3d at 1290 (internal citation omitted).

Abbott Labs.,
Moreover, BMS

distinguishes Abbott Labs. because the district court there
44

rested the decision to limit the patent on the fact that “the
rest of the intrinsic evidence, including the prosecution
history and the priority [] application, evince[d] a clear
intention to limit the ‘507 patent to Crystal A as defined by
the seven PXRD peaks in the specification and in claim 1.”

Id.

(See Pl. Responsive Br. at 14-15.)
The Court has considered the parties’ respective arguments,
the patent claims, the specification, the prosecution history
and the expert evidence.

The Court agrees with the patentee

that the term should not be limited by the example described in
the specification or by the analytical test results used to
specify structural information about the crystalline
monohydrate.

The Court thus construes the term “Crystalline

monohydrate of the compound of formula

(IV)

” as follows:
The monohydrate of the compound of formula (IV) in a

crystalline form.

45

2.

“Which is characterized by an x-ray powder
diffraction pattern substantially in accordance
with that shown in FIG. 1”

The term appears in claim 1 of the ‘725 Patent.
Patent at col. 48, lines 62-63.)

(See ‘725

BMS proposes a construction as

follows: “which is characterized by an x-ray powder diffraction
pattern that is substantially identical to those shown in FIG. 1
taking into account variations due to measurement errors and
dependent upon the measurement conditions employed, but not
taking into account the exact order of intensity of the peaks.”
(Joint Statement at 34.)

BMS also notes that it considers “the

ability to ascertain substantial identities of X-ray diffraction
patterns [to be] within the purview of one of ordinary skill in
the art.”

(Id.)

BMS points to statements in the specification

that “[a]ny crystal forms that provide X-ray diffraction
patterns substantially identical to those disclosed in the
accompanying Figures fall within the scope of the present
invention.

The ability to ascertain substantial identities of

X-ray diffraction patterns is within the purview of one of
ordinary skill in the art.”
13.)

(‘725 Patent at col. 42, lines 8-

Further, the specification discloses:
One of ordinary skill in the art will appreciate that
an X-ray diffraction pattern may be obtained with a
measurement error that is dependent upon the
measurement conditions employed. In particular, it is
generally known that intensities in an X-ray
diffraction pattern may fluctuate depending upon
46

measurement conditions employed. It should be further
understood that relative intensities may also vary
depending upon experimental conditions, and
accordingly, the exact order of intensity should not
be taken into account. Additionally, a measurement
error of diffraction angle for a conventional X-ray
diffraction pattern is typically about 5% or less, and
such degree of measurement error should be taken into
account as pertaining to the aforementioned
diffraction angles. Consequently, it is to be
understood that the crystal forms of the instant
invention are not limited to the crystal forms that
provide X-ray diffraction patterns completely
identical to the X-ray diffraction patterns depicted
in the accompanying Figures disclosed herein.
(Id. at col. 41, line 58 to col. 42, line 8.)

BMS argues that

its construction accounts for the variations in test results
that a person of ordinary skill in the art would recognize are
normally attributable to measurement errors or conditions.
Pl. Opening Br. at 20.)

(See

The Court of Appeals for the Federal

Circuit has previously deemed the term “substantially” a
“descriptive term[] commonly used in patent claims to avoid a
strict numerical boundary to the specified parameter”.

See

Playtex Prods., Inc. v. Procter & Gamble Co., 400 F.3d 901, 907
(Fed.Cir. 2005).

Additionally, BMS argues that “the patent

teach[es] that peak intensities may fluctuate and the exact
order of intensity of the peaks should not be considered in
comparing X-ray diffraction patterns.”

(Pl. Opening Br. at 20

(citing ‘725 Patent at col. 41, line 58 to col. 42, line 13).)

47

Apotex proposes the following construction: “[t]he product
being characterized much match the x-ray powder diffraction
pattern presented in FIG. 1 of the patent specification, and
further do so in such a way so as to uniquely identify the
referenced ‘[c]rystalline monohydrate of the compound of formula

(IV)
34.)

.”

(Joint Statement at

Apotex argues that BMS’s definition of “substantially”

vitiates the term and impermissibly broadens the scope of the
claim beyond the “one specific ‘crystalline monohydrate’ and . .
. XRPD ‘fingerprint’ shown in Figure 1 of the ‘725 patent” that
BMS chose to claim.

(Defs. Opening Br. at 25.)

To oppose BMS’s

suggestion that the exact order of peak intensity should not be
taken into account, Apotex relies on an expert to argue that
“even slight differences in an XRPD pattern can result in an
inability to uniquely identify the substance being considered.”
(Id. at 26.)

Further, Apotex argues that an XRPD pattern that

was “substantially identical” to those in Figure 1 would leave a
person of ordinary skill in the art without confidence that the

48

product tested is in fact the patented “[c]rystalline
monohydrate of the compound of formula (IV).”

(Id.)

BMS responds to Apotex’s argument by pointing out that
Apotex can find no intrinsic evidence to support the
construction that “the product being characterized must match
the x-ray powder diffraction pattern presented in FIG. 1 of the
patent specification”.

(Pl. Responsive Br. at 16.)

BMS also

points out that Apotex’s expert contradicts this definition by
testifying that “substantially in accordance” does not mean
“must match” but rather “matches well”.

(See id.)

Additionally, the expert recognizes that XRPD results can have
measurement errors and can result in two x-ray diffraction
patterns having different intensities but yet representing the
same crystalline material.

(See id. at 17.)

Apotex in its

response renews its arguments regarding the linguistic
ambiguities inherent in the terms “substantially in accordance”
or “substantially identical.”

(See Defs. Responsive Br. at 21-

24.)
The Court has considered the parties’ respective arguments,
the patent claims, the specification and the expert evidence.
The Court agrees with the patentee that the term “substantially
in accordance” should not be construed so strictly as to unduly
narrow the scope of the claim.

Furthermore, the Court rejects
49

the extrinsic testimonial evidence of Apotex’s expert in favor
of the teachings of the patent concerning importance of peak
intensities.

The Court thus construes the term “which is

characterized by an x-ray powder diffraction pattern
substantially in accordance with that shown in FIG. 1” as
follows:
Which is characterized by an x-ray powder diffraction
pattern that is substantially identical to those shown in FIG. 1
taking into account variations due to measurement errors and
dependent upon the measurement conditions employed, but not
taking into account the exact order of intensity of the peaks.

3.

“The compound of claim 1” or “The compound of
claim 3” or “A process for preparing the compound
of claim 3” or “The compound of claim 9” or “the
compound of claim 12”

These terms appear in claims 2, 4-11, and 13-16 of the ‘725
Patent, which depend directly or indirectly from claims 1, 3, or
12.

(See, e.g., ‘725 Patent, col. 49, lines 39-40.)

The

parties’ arguments and constructions of the terms will be
separately treated by the Court in analysis and construction.

50

a.

“The compound of claim 1” or “The compound
of claim 3” or “The compound of claim 9” or
“the compound of claim 12”

BMS proposes that the term used in claims 2, 4, 5, 8-11,
and 13-16 be given its plain meaning as understood by a person
of ordinary skill in the art, namely, “the crystalline
monohydrate of the compound of formula (IV).”
at 35.)

(Joint Statement

Apotex would have the term in claim 2 mean: “[t]he

compound defined by claim 1, including all limitations of claim
1.”

(Id.)

As used in claims 4, 5, 8-10, and 13, Apotex

proposes the claim be construed as “[t]he compound that is
identified and defined as such in claim 3; [which in turn is
identified in claim 9]; this construction renders claim [4,5, 8,
9, 10] invalid for improper dependency.”

(Joint Statement at 39

(noting also that “[t]o the extent the claim is construed as
limited to a particular crystal form, the claim is not enabled
and/or not infringed because the crystal form no longer exists
if it is to engage in any therapeutic activity.”), 41, 43, 46,
47, 50.)

As used in claims 14-16, Apotex requests that the

Court construe the term to mean “the compound that is identified
and defined as such in claim [9, 12]; this construction renders
claim [14, 15, 16] invalid for improper dependency.”
Statement at 50, 51, 52.)

51

(Joint

BMS argues succinctly that the Court should construe the
term to mean “the plain and ordinary meaning of the phrase as
understood by one of skill in the art based on the
specification, namely the monohydrate of the compound of formula
IV in a crystalline form.”

(Pl. Opening Br. at 21.)

As an

illustrative example, BMS points to claim 2, which recites a
compound of claim 1 characterized by a differential scanning
calorimetry thermogram substantially in accordance with FIG. 2.
(See ‘725 Patent at col. 48, lines 64-67.)

BMS further notes

that FIG. 2 displays “a DSC and TGA of ‘the monohydrate of the
compound of Formula (IV).’”

Thus, BMS argues that, when the

specification and claims are read in context, the term means
“the monohydrate of the compound of formula IV in a crystalline
form.”

(Pl. Opening Br. at 22 (citing Phillips, 415 F.3d at

1314; Pause Tech. LLC v. TiVo, Inc., 419 F.3d 1326, 1331
(Fed.Cir. 2005) (“proper claim construction . . . demands
interpretation of the entire claim in context, not a single
element in isolation.”)).)

BMS finally argues that Apotex’s

proposed constructions do not qualify as constructions of
claims, but rather as “arguments concerning the validity of the
claims”, finding no support in either the claim language or the
patent specification.

(See Pl. Opening Br. at 22.)

52

Apotex argues that the specification teaches there is a
difference between “crystalline monohydrate” and a “compound”:
“The compound of formula (IV) . . . is an inhibitor of SRC/ABL
and is useful in the treatment of oncological diseases.”
Patent at col. 1, lines 51-65.)

(‘725

In another section, the

specification notes that “another aspect” of the invention is
“crystalline forms of the compound of formula (IV).”
col. 4, lines 55-56.)

(Id. at

Apotex argues that, by distinguishing

between the crystalline form and the compound, the specification
teaches that “a compound of Formula IV can exist in multiple
iterations (such as in solution) in a manner distinct from the
monohydrate structure (since a monohydrate structure is a
creature of the solid phase, not the liquid phase).”

(Defs.

Opening Br. at 36.)
The Court has considered the parties’ respective arguments,
the patent claims, and the specification.

The Court agrees with

the patentee that the term “the compound of claim [1, 3, 9, 12]”
is not insolubly ambiguous so as to render the claim invalid.
Furthermore, the Court finds that a person of ordinary skill in
the art could rely on the teachings of the patent as a whole
concerning the meaning of the terms.

From reading the ‘725

Patent as a whole, a person of ordinary skill would understand
that the subject of these claims is properly the crystalline
53

monohydrate.

The Court thus construes the term “[t]he compound

of claim 1” or “[t]he compound of claim 3” or “[t]he compound of
claim 9” or “the compound of claim 12” as follows:
The monohydrate of the compound of formula (IV) in a
crystalline form.

b.

“A process for preparing the compound of
claim 3”

BMS proposes the term as used in claims 6 and 7 be given
its plain meaning as understood by a person of ordinary skill in
the art: “a process for preparing the crystalline monohydrate of
the compound of formula (IV).”

(Joint Statement at 40.)

BMS

did not differentiate between this term and those immediately
preceding so, with respect to this term, BMS made no separate
arguments in its opening papers.

(See Pl. Opening Br. at 21.)

Apotex argues that the term should be construed so that the
process addressed “must occur in the United States for
preparing.”

(Joint Statement at 40.)

Apotex also argues that

the term is vague and indefinite in the context of the claim.
(See id.)

Apotex notes that these claims are directed to “‘[a]

process for preparing the compound of claim 3’ comprising
heating, dissolving, and crystallizing steps and specifying
various parameters.”

(Defs. Opening Br. at 34.)

54

Relying on 35

U.S.C. § 271(a), Apotex argues that, with respect to
infringement of a process claim, any allegedly infringing act
must occur inside the United States in order to support a
finding of infringement.

(See id. at 35.)

BMS rejects Apotex’s argument in reply, noting that Apotex
has not offered a construction, but rather argued about where
any infringement may occur.

(See Pl. Responsive Br. at 26.)

BMS notes that there is no intrinsic evidence to suggest the
process was restricted to the United States, nor does case law
preclude a patented product made outside the United States, but
later imported into the country, from potentially infringing a
patent.

(See id.)

The Court has considered the parties’ respective arguments,
the patent claims and the specification.

The Court agrees with

the patentee that neither case law nor the intrinsic evidence of
the patents require the term “[a] process for preparing the
compound of claim 3” to signify that the “process” occur in the
United States.

The Court thus construes the term “[a] process

for preparing the compound of claim 3” as follows:
A process for preparing the crystalline monohydrate of the
compound of formula (IV).

55

4.

“Which is characterized by differential scanning
calorimetry thermogram and a thermogravimetric
analysis substantially in accordance with that
shown in FIG. 2”; “[being further] characterized
by a differential scanning calorimetry having a
broad peak between approximately 95° C and
130° C”; “wherein the differential scanning
calorimetry further has a peak at approximately
287° C”

Although the parties separate the terms in the Joint
Statement, Apotex has addressed the three terms simultaneously
and BMS too overlaps its proposed constructions.

(See Joint

Statement at 36, 44, 48; Pl. Opening Br. at 22, 27, 30; Defs.
Opening Br. at 30.)

Accordingly the Court will set forth the

proposed constructions separately but provide the parties’
arguments and the Court’s construction of the terms together.
a.

“Which is characterized by differential
scanning calorimetry thermogram and a
thermogravimetric analysis substantially in
accordance with that shown in FIG. 2”

The term “[w]hich is characterized by differential scanning
calorimetry thermogram and a thermogravimetric analysis
substantially in accordance with that shown in FIG. 2” appears
in claim 2 of the ‘725 Patent, which depends directly on
claim 1.

(See ‘725 Patent, col. 48, line 64.)

BMS proposes that the term be construed to mean the
following:
Which is characterized by differential scanning
calorimetry thermogram and thermogravimetric analysis
56

patterns that are substantially identical to those
shown in FIG. 2, having one peak at approximately 287°
C and one broad peak between approximately 95° C and
approximately 130° C. The ability to ascertain
substantial identities of patterns is within the
purview of one of ordinary skill in the art.
(Joint Statement at 36.)

Apotex proposes:

The product being characterized must match both the
differential scanning calorimetry thermogram and the
thermogravimetric results presented in FIG. 2 of the
patent specification, and further do so in such a way
as to uniquely identify the referenced “[c]rystalline
monohydrate of the compound of formula (IV)

. . . .”
At least the phrase “differential scanning calorimetry
thermogram . . . in accordance with that shown in FIG.
2” is indefinite owing to the failure, in the patent
specification to disclose the methodology for testing.
(E.g., open pan, first run/second run).
(Id.)
b.

“[Being further] characterized by a
differential scanning calorimetry having a
broad peak between approximately 95° C and
130° C”

The term “[being further] characterized by a differential
scanning calorimetry having a broad peak between approximately
95° C and 130° C” appears in claims 9 and 12 of the ‘725 Patent.
(See id. at col. 50, lines 1-3, 25-26.)

57

BMS proposes the term be construed to mean: “being further
characterized by a differential scanning calorimetry having a
broad peak between about 95° C and about 130° C.

This peak can

be variable but corresponds to the loss of one water of
hydration on thermogravimetric analysis.”
44.)

(Joint Statement at

Apotex’s proposed construction is as follows:
The product being characterized must match the stated
results.
The term “broad peak” is vague and indefinite. The
term “peak” is not routinely used in the context of
analyzing differential scanning calorimetry data. To
the extent the term is intended to refer to endotherms
or exotherms that can appear in a DSC trace, the claim
language is indefinite and/or non-enabled.
“Approximately” is indefinite in the context of the
claims.
At least the phrase “differential scanning
calorimetry” is indefinite owing to the failure to
disclose the methodology for testing. (E.g., open
pan, first run/second run).

(Id.)
c.

“Wherein the differential scanning
calorimetry further has a peak at
approximately 287° C”

The term “wherein the differential scanning calorimetry
further has a peak at approximately 287° C” appears in claim 11
of the ‘725 Patent.

(See id. at col. 50, lines 10-11.)

BMS proposes the term be construed to mean “characterized
by differential scanning calorimetry with a peak located at
about 287° C which corresponds to the melt of the dehydrated

58

form of the compound of formula (IV).”

(Joint Statement at 48.)

Apotex proposes the term be construed as follows:
The product being characterized must match the stated
results.
The term “broad peak” is vague and indefinite. The
term “peak” is not routinely used in the context of
analyzing differential scanning calorimetry data. To
the extent the term is intended to refer to endotherms
or exotherms that can appear in a DSC trace, the claim
language is indefinite and/or non-enabled.
“Approximately” is indefinite in the context of the
claims.
At least the phrase “differential scanning
calorimetry” is indefinite owing to the failure to
disclose the methodology for testing. (E.g., open
pan, first run/second run).
(Id.)
d.

Arguments and Construction

BMS argues that its proposed constructions of the terms are
supported by the specification as it would be understood by a
person of ordinary skill in the art.
23.)

(See Pl. Opening Br. at

The ‘725 Patent includes language describing the graphical

depiction in FIG. 2, which mirrors BMS’s proposed construction
for the terms:
The monohydrate of the compound of formula (IV) is
represented by the DSC as shown in FIG. 2. The DSC is
characterized by a broad peak between approximately
95° C. and 130° C. This peak is broad and variable
and corresponds to the loss of one water of hydration
as seen in the TGA graph. The DSC also has a
characteristic peak at approximately 287° C. which
corresponds to the melt of the dehydrated form of the
compound of formula (IV).

59

(‘725 Patent at col. 45, lines 15-22.)

BMS also notes that one

of ordinary skill in the art would recognize that inherent
measurement errors and conditions may cause variations, and thus
would take those factors into account when ascertaining the
substantial identities of differential scanning calorimetry or
thermogravimetric analysis patterns.
23.)

(See Pl. Opening Br. at

Finally, BMS argues that Apotex’s construction would

improperly write “substantially in accordance” out of the claim
in contravention of the plain language of the claim and the
teachings of the specification.

See Bicon, Inc. v. Straumann

Co., 441 F.3d 945, 951-52 (Fed.Cir. 2006).
Apotex argues that one ordinarily skilled in the art would
be unable to understand the meaning of the terms.
Opening Br. at 30.)

(See Defs.

Apotex makes four arguments regarding

confusion: (1) one skilled in the art would be confused about
how to perform the differential scanning calorimetry test
without the patent teaching the methodology for conditions and
related variables; (2) “substantially in accordance” fails to
sever the claims from the particularly described monohydrate
crystal as set forth in the specification, even if BMS wants to
broaden the scope of the claim (to also encompass other
hydrates, compounds or excipients); (3) a person of ordinary
skill in the art would not describe differential scanning
60

calorimetry data outputs with the term “peak”, giving it no
“plain meaning” in this context; and (4) words of degree like
“broad peak”, “approximately 95° C and 130° C” or “approximately
287° C” inhibit the guidance or standards that a person of
ordinary skill in the art would need to properly quantify the
breadth of the peak in differential scanning calorimetry
patterns.

(See id. at 31-32.)

BMS responds that Apotex’s assertions of insoluble
ambiguity are wrong because: (1) sufficient instructions were
provided for one of ordinary skill in the art to replicate the
experimental conditions used by the inventors (see, e.g., ‘725
Patent at col. 43, lines 1-22.); (2) Apotex is merely abandoning
a construction of the term in claim 2 that was unsupported by
its expert, who stated that “substantially in accordance” does
not mean “must match”; (3) the term does not broaden the scope
of the claim to other hydrates, compounds, or excipients because
it explicitly limits itself to “the crystalline monohydrate of
the compound of formula (IV)”; (4) “peak” is known and used in
the art, as demonstrated by the testimony of the experts for
both BMS and Apotex; and (5) Apotex’s own expert understood that
“broad peak between approximately 95° C and 130° C” corresponded
to the loss of one water of hydration and that errors associated
with testing could make the use of “approximately” appropriate
61

in this context.

(See Pl. Responsive Br. at 21-23.)

Apotex, in

response and at oral argument, argues that the insoluble
ambiguity of the claims would prevent one of ordinary skill in
the art from understanding the claim.

(See Defs. Responsive Br.

at 26-28; 9-10-12 Transcript at 67, line 5 to 70, line 17.)
The Court has considered the parties’ respective arguments,
the patent claims, the specification, and the experts’
testimonial evidence.

The Court agrees with the patentee that

the ability to ascertain substantial identities of patterns is
within the purview of one of ordinary skill in the art and that
the specification’s instructions disclose sufficient guidance to
permit replication of the methodology.

The Court also finds

that the term “substantially in accordance” does not require
that analysis of the product being characterized must
identically match the results as stated in the figure.

The

Court thus construes the terms “[w]hich is characterized by
differential scanning calorimetry thermogram and a
thermogravimetric analysis substantially in accordance with that
shown in FIG. 2”, “[being further] characterized by a
differential scanning calorimetry having a broad peak between
approximately 95° C and 130° C” and “wherein the differential
scanning calorimetry further has a peak at approximately 287° C”
as follows:
62

Which is characterized by differential scanning calorimetry
thermogram and thermogravimetric analysis patterns that are
substantially identical to those shown in FIG. 2, having one
peak at approximately 287° C and one broad peak between
approximately 95° C and approximately 130° C.
Being further characterized by a differential scanning
calorimetry having a broad peak between about 95° C and about
130° C.
Characterized by differential scanning calorimetry with a
peak located at about 287° C which corresponds to the melt of
the dehydrated form of the compound of formula (IV).

5.

“[W]hich is characterized by an x-ray powder
diffraction pattern (CuKα λ=1.5418 Å at a
temperature of about 23°C.) comprising four or
more 2θ values selected from the group consisting
of 18.0±0.2, 18.4±0.2, 19.2±0.2, 19.6±0.2,
21.2±0.2, 24.5±0.2, 25.9±0.2, and 28.0±0.2”

The term appears in claim 3 of the ‘725 Patent.

(See ‘725

Patent, col. 49, lines 14-18.)
BMS proposes that the term be given its plain meaning as
understood by one of ordinary skill in the art.

Accordingly,

BMS would have the term stand as is. (See Joint Statement at
38.)

Apotex would have the Court construe the term as follows:
The product being characterized must uniquely identify
the referenced “[c]rystalline monohydrate of the
compound of formula (IV)”
63

And generate an x-ray powder diffraction pattern using
the methodology provided (CuKα λ=1.5418 Å at a
temperature of about 23°C).
The term “2θ values” is vague and indefinite.
“selected from the group consisting of” is Markush
language, but in the context of the claims is vague
and indefinite; [sic]
To the extent variance is permitted, it is not
supported by the claims; is indefinite and not
supported by the written description; and violates the
Markush concept.
(Id.)
BMS argues that the term is unambiguous and well-understood
by those of ordinary skill in the art as written.
Opening Br. at 24.)

(See Pl.

BMS contrasts its suggested definition with

that proposed by Apotex and notes that Apotex seeks to import
limitations into the term that are not supported by the
specification or any other intrinsic evidence.

(See id. at 24-

25.)
Apotex argues that this claim can only cover “one unique
type of crystal . . . produced according to the specification
procedures.”

(Defs. Opening Br. at 27.)

This claimed crystal

must have all the peaks noted in the claim and many others,
making the language in the term redundant and perhaps even
excluding the very crystal supposedly claimed under the patent.
(See id. at 27-28.)

Apotex also argues that this allows BMS to

claim other materials with some of the peaks described, but not
all that the crystal would have.
64

(See id. at 28.)

Finally,

Apotex argues that the variance of “±0.2” is unsupported by the
specification.

(See id.)

The Court has considered the parties’ respective arguments,
the patent claims, the specification, and the experts’
testimonial evidence.

The Court agrees with the patentee that

the ability to ascertain substantial identities of patterns is
within the purview of one of ordinary skill in the art and that
the instructions provided in the specification are sufficient
guidance to permit replication of the methodology.

The Court

also finds that the term “substantially in accordance” does not
require that analysis of the product being characterized must
identically match the results as stated in the figure.

The

Court is unpersuaded by Apotex’s argument against the “±0.2”
variance, noting that Apotex does not offer the testimony of an
expert to counter BMS’s expert’s contention that the peaks were
tethered to the monohydrate in the specification and that such
variances were commonly used by persons of ordinary skill in the
art.

The Court thus construes the term “[w]hich is

characterized by differential scanning calorimetry thermogram
and a thermogravimetric analysis substantially in accordance
with that shown in FIG. 2” as follows:
Which is characterized by an x-ray powder diffraction
pattern taken with CuKα λ=1.5418 Å at a temperature of about
65

23°C, having at least four 2θ values selected from the group
consisting of 18.0±0.2, 18.4±0.2, 19.2±0.2, 19.6±0.2, 21.2±0.2,
24.5±0.2, 25.9±0.2, and 28.0±0.2.
6.

“[C]haracterized by unit cell parameters
approximately equal to the following dimensions:
Cell dimensions: a(Å)=13.8632(7); b(Å)=9.3307(3);
c(Å)=38.390(2); Volume=4965.9(4) Å3
Space group Pbca
Molecules/unit cell 8
Density (calculated) (g/cm3) 1.354”

The term appears in claim 5 of the ‘725 Patent.

(See ‘725

Patent at col. 49, lines 23-32.)
BMS proposes that the term be given its plain meaning as
understood by one of ordinary skill in the art.
Statement at 40; Pl. Opening Br. at 25.)

(See Joint

Apotex raised

indefiniteness and written description invalidity defenses to
this claim language, but fails to offer the Court a proposed
definition: “Apotex respectfully submits that this language is
insolubly ambiguous, unsupported and not capable of being
construed.”

(Defs. Opening Br. at 29 n.9, 30; see Joint

Statement at 40.)

Apotex argues that the term is too precisely

rendered to refer to “anything but a specially-grown single
crystal; there is no standard for ‘approximately equal.’”
(Defs. Opening Br. at 29.)
BMS responds that the term “approximately equal” is
unambiguous and well-understood by those of ordinary skill in
66

the art as written.

(See Pl. Opening Br. at 20.)

BMS contrasts

testimony from Apotex’s expert about the confusion from
“approximately equal” with the same expert’s suggestion for a
meaningful substitution: “approximately the same”.
20-21.)

(See id. at

BMS also rebuts Apotex’s argument that the unit cell

parameters listed in the claim could not be achieved if the
compound was in powder form, as would be required for other
elements of the claim.

(See id.)

Apotex’s expert testified

that the tests in the claim could produce the results as
written, which undermines the argument that the language is
ambiguous because it would not be understood by a person of
ordinary skill in the art.

(See id.)

BMS asserts that these

semantics-based or purely attorney arguments cannot overcome the
plain language of the claim.

(See id.)

Apotex renews its arguments regarding the different
preparations of the compound for the tests and indefiniteness of
the term in its response.

(See Defs. Responsive Br. at 25-26.)

BMS cited, inter alia, Merck & Co. v. Teva Pharm. U.S.A., Inc.,
395 F.3d 1364, 1372 (Fed.Cir. 2005), where the court had
construed “approximately” to mean “about”.

Apotex argues that

the parties there had stipulated to a definition of the term and
that the case is less relevant than Amgen, which invalidated a
claim containing the phrase “at least about 160,000” for
67

indefinite limitation.

See Amgen, Inc. v. Chugai Pharm. Co.,

927 F.2d 1200, 1218 (Fed.Cir. 1991).
at 26.)

(See Defs. Responsive Br.

The Court is unpersuaded by Apotex’s reading of the

case cited.

In Amgen, the court determined that the claim was

invalid based on, inter alia, the prosecution history of the
patent in question:
When the examiner noticed this disclosure late in the
prosecution, he rejected the ‘195 claims with a
specific activity limitation of “at least 120,000” as
anticipated by the Miyake et al. disclosure. It was
only after the “at least 120,000” claims were
cancelled that [the patentee] submitted the “at least
about 160,000” claim language.
The [district] court found the “addition of the word
‘about’ seems to constitute an effort to recapture . .
. a mean activity somewhere between 120,000, which the
patent examiner found was anticipated by the prior
art, and [the] 160,000 IU/AU” claims which were
previously allowed. Because “the term ‘about’ 160,000
gives no hint as to which mean value between the
Miyake et al. value of 128,620 and the mean specific
activity level of 160,000 constitutes infringement,”
the court held the “at least about” claims to be
invalid for indefiniteness. This holding was further
supported by the fact that nothing in the
specification, prosecution history, or prior art
provides any indication as to what range of specific
activity is covered by the term “about,” and by the
fact that no expert testified as to a definite meaning
for the term in the context of the prior art. In his
testimony, Fritsch tried to define “about” 160,000,
but he could only say that while “somewhere between
155[,000] might fit within that number,” he had not
“given a lot of direct considerations to that. . . .”

Amgen, 927 F.2d at 1217-18.

68

The Court has considered the parties’ respective arguments,
the patent claim, the specification, and the experts’
testimonial evidence.

The Court agrees with the patentee that

“approximately equal” is unambiguous and well-understood by
those of ordinary skill in the art, and that the instructions
provided in the specification provide sufficient guidance to
permit an expert to reproduce the results specified in the term.
The Court thus construes the term “characterized by unit cell
parameters approximately equal to the following dimensions:
Cell dimensions: a(Å)=13.8632(7); b(Å)=9.3307(3);
c(Å)=38.390(2);
Volume=4965.9(4) Å3
Space group Pbca
Molecules/unit cell 8
Density (calculated) (g/cm3) 1.354” as follows:
“[C]haracterized by unit cell parameters approximately
equal to the following dimensions:
Cell dimensions: a(Å)=13.8632(7); b(Å)=9.3307(3);
c(Å)=38.390(2);
Volume=4965.9(4) Å3
Space group Pbca
Molecules/unit cell 8
Density (calculated) (g/cm3) 1.354”
69

7.

“Wherein the compound is substantially pure”

The term appears in claims 8, 15, and 16 of the ‘725
Patent, which depend directly or indirectly on either claim 3 or
12.

(See, e.g., ‘725 Patent, col. 48, line 64.)
BMS proposes that the term be construed to mean: “[t]he

compound itself having a purity greater than 90 percent.

The

‘substantially pure’ compound may be employed in pharmaceutical
compositions to which other desired components are added, for
example excipients, carriers, or active chemical entities of
different molecular structure.”

(Joint Statement at 42.)

Apotex contends that the term is indefinite, particularly in
light of the claim language.

(Id.)

BMS argues that the language of the patent specification
provides the definition of this term: “[t]he present invention
describes crystalline forms of the compound of formula (IV) in
substantially pure form.

As used herein, ‘substantially pure’

means a compound having a purity greater than 90 percent,
including 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, and 100
percent.”

(‘725 Patent at col. 15, lines 26-30.)

The

specification further describes an example of a crystalline form
of the compound of formula (IV) as being “substantially pure”
when it has “a purity greater than 90 percent, where the
remaining less than 10 percent of material comprises other
70

form(s) of the compound of the formula (IV), and/or reaction
and/or processing impurities arising from its preparation.”
(Id. at col. 15, lines 28-40.)

BMS argues that the intrinsic

evidence of the terms meaning should control the Court’s
construction.

(See Pl. Opening Br. at 26-27.)

Apotex argues, based on Stedman’s® Medical Dictionary, that
a compound is “a substance formed by the covalent or
electrostatic union of two or more elements, generally differing
entirely in physical characteristics from any of its
components.”

(Defs. Opening Br. at 24.)

Thus, Apotex argues, a

compound structure cannot have degrees of purity because its
identity will be completely dictated by the precise relative
ratios of its individual components.

(See id.)

Moreover,

Apotex argues that the term is too indefinite to provide
meaningful guidance to one of ordinary skill in the art because
it fails to provide the exact nature of the percentage, purity
not being an element or known compound of which the exact
presence can be calculated.

(See id.)

Hence, without an

indication that the patent inventors intended purity by weight
percent, volume percent, or molar percent, the missing units of
purity prevent one of ordinary skill the art from understanding
this term.

(See id. at 23-24.)

71

BMS counters that Apotex’s expert understood the meaning of
the term, and that he testified that a person of ordinary skill
in the art could understand what the term indicated in the full
context of the patent.

(See Pl. Responsive Br. at 15.)

Additionally, BMS’s expert indicated that, taken as a whole,
“the ‘725 patent would have taught one of ordinary skill in the
art that the purity of the crystalline monohydrate of the
compound of formula (IV) [should] be measured by weight
percent.”

(See id.; see also dkt. entry no. 67, Supp. Decl. of

Jerry Atwood at 2-3.)

Finally, BMS argues that the use of terms

such as “pure” and “substantially pure” is recognized and
supported by case law.

(See id. at 15-16 (citing cases).)

Apotex opposes BMS’s constructions with renewed arguments
that the patent does not define “substantially pure” clearly
enough to avoid invalidation for indefiniteness.

(See Defs.

Responsive Br. at 19-21.)
The Court has considered the parties’ respective arguments,
the patent claims, the specification, and the experts’
testimonial evidence.

The Court agrees with the patentee that

the instructions in the specification provide sufficient
guidance to permit one with ordinary skill in the art to
determine whether a substance is “substantially pure”.

The

Court agrees with the patentee that a “substantially pure”
72

sample of the compound may contain a small amount of material
made up of the compound, but which is present in a different
form from the crystalline form of the monohydrate, or which is
derived from processing or reaction impurities.

Moreover, the

“substantially pure” compound may be employed in pharmaceutical
compositions to which other desired components are added, e.g.,
excipients, carriers, or active chemical entities of different
molecular structure.

The Court thus construes the term “wherein

the compound is substantially pure” as follows:
“The compound itself having a purity greater than 90
percent.”

8.

“[W]hich corresponds to the loss of one water of
hydration on thermogravimetric analysis”

The term appears in claims 9 and 12 of the ‘725 Patent.
(See, e.g., ‘725 Patent, col. 50, lines 3-5.)
BMS proposes that the term be construed to mean “which
corresponds to a weight loss attributable to one water of
hydration on thermogravimetric analysis.”
45.)

(Joint Statement at

Apotex requests that the Court find the term “makes no

sense in context, because a ‘compound’ does not lose water.”
(Id.)

If the Court does not find the language “internally

contradictory,” Apotex asks the Court to recognize that “the

73

language out of context would indicate that there is a peak in
the DSC that must correspond and otherwise perfectly align to a
TGA test result on the same sample being tested in which a
precise, specific ratio of molecule(s) of water that constituted
water formally associated in the unit cell of a crystal lattice
is released (e.g., lost) in the specified test period.”

(Id.)

BMS relies on the testimony of its expert to explain that
“one of ordinary skill would understand this term to mean that
the broad peak between approximately 95°C and 130°C corresponds
to a weight loss attributable to one water of hydration on
thermogravimetric analysis.”

(Pl. Opening Br. at 28.)

Apotex informs the Court that “[t]hermogravimetric analysis
(“TGA”) is a technique that measures change in the weight of a
sample as a function of temperature.

(Desiraju ¶ 66).

Such a

change might indicate to one of skill in the art that residual
solvent, such as water, is lost, perhaps confirming the presence
of that solvent.”

(Defs. Opening Br. at 33.)

Apotex argues

that the “loss of one water of hydration on thermogravimetric
analysis” does not correspond with “the output of the test
method”, rendering the claim language insolubly ambiguous.
id.)

Moreover, Apotex argues that a “compound of claim 3”

cannot lose one water of hydration because the Formula IV
structure (which is the compound of claim 3) would be
74

(See

fundamentally altered if such an event occurred, and it would
become a decomposition product.

(See id.)

Finally, Apotex

argues that claim 9 refers to results from both differential
scanning calorimetry and thermogravimetric analysis tests, which
are mutually exclusive -- performing either test will destroy
the tested material, making it impossible to then serially
perform the other test.

(See id. at 34.)

BMS explained at oral argument that thermogravimetric
analysis is destructive testing that will destroy a crystalline
monohydrate piece by piece to determine its component parts
through physical chemistry testing.

(See dkt. entry no. 92, Tr.

of Markman Hr’g on Oct. 2, 2012 at 97-100 (“10-2-12
Transcript”).)
MS. BEN-AMI: For each molecule of Dasatinib there’s
only one water. So if there’s 100 percent, you know -if the experiment is 100 percent perfect in theory,
which no experiments are, then you would say all the
water was out at that time.
THE COURT: Okay. But some may be a little bit
reluctant -MS. BEN-AMI: But you’ve got the concept correct that
water is coming off at one temperature. The rest of it
is melting at a different temperature. That’s,
basically, what it is about.
(Id. at 99-100.)

Further, with respect to Apotex’s position

that the term is confusing because “compound” is not the
crystalline monohydrate, BMS contends that experts for both
parties understood the meaning of the word in this context and
75

in light of the patent as a whole.
24.)

(See Pl. Responsive Br. at

BMS notes particularly that Figure 2 shows both

differential scanning calorimetry and thermogravimetric analysis
thermograms of the crystalline monohydrate of the compound of
formula (IV).

(See id.)

As the claim’s reference, this

furthers BMS’s argument that a person of ordinary skill in the
art would understand the word “compound” to mean the test had
been performed on the crystalline monohydrate.

(See id.)

Apotex responds with several arguments: (1) without any
intrinsic support for such an assumption, BMS presumes that
“compound”, which does not have a water of hydration to lose,
means “crystalline monohydrate”, which is accompanied by a water
for each chemical structure; and (2) BMS ignores the requirement
that the “peak” observed in the differential scanning
calorimetry analysis correspond with the loss of the water of
hydration.

(See Defs. Responsive Br. at 28-29.)

The Court has considered the parties’ respective arguments,
the patent claims, the specification and the experts’
testimonial evidence.

The Court agrees with the patentee that

one of ordinary skill would understand this term to mean that
the broad peak between approximately 95°C and 130°C corresponds
to a weight loss attributable to one water of hydration on
thermogravimetric analysis.

The Court also finds that the term
76

“compound of claim 3” does not create insoluble ambiguity in
light of the graph in Figure 2 of the specification, which shows
both differential scanning calorimetry and thermogravimetric
analysis thermograms of the crystalline monohydrate of the
compound of formula (IV).

The Court thus construes the term

“which corresponds to the loss of one water of hydration on
thermogravimetric analysis” as follows:
“[W]hich corresponds to a weight loss attributable to one
water of hydration on thermogravimetric analysis.”

9.

“[W]hich is further characterized by a weight
loss of 3.48% by thermogravimetric analysis
between 50° C and 175° C”

The term appears in claim 10 of the ‘725 Patent.

(See ‘725

Patent, col. 50, lines 6-8.)
BMS proposes that the term be construed to mean “which is
further characterized by a weight loss of 3.48% by
thermogravimetric analysis between 50° C and 175° C, taking into
account variations due to measurement errors and dependent upon
the measurement conditions employed.”

(Joint Statement at 46.)

Apotex states that “[i]n isolation, the phrase would refer
to material that is being subjected to the testing.

(Id.)

If

the Court does not find the language “internally contradictory,”
Apotex asks the Court to recognize that “the language out of
77

context would indicate that there is an instrumental measured
weight loss of the stated amount being sampled between the
stated temperature range.

However, this claim language is vague

and indefinite in the context of the remainder of the claim.
The ‘weight loss’ claim language makes no sense in context, or
is not enabled, because a ‘compound’ does not lose weight.”
(Id.)
BMS points to support from the specification for its
proposed construction: “[t]he TGA shows a 3.48% weight loss from
50 C to 175 C.

The weight loss corresponds to a loss of one

water of hydration from the compound of Formula (IV).”

(Pl.

Opening Br. at 29; ‘725 Patent at col. 45, lines 25-28.)
Apotex complains that the “material that is supposedly
supposed to lose the weight is ‘the compound of claim 9.’ . . .
[T]he compound structure of Formula (IV) is not going to lose
water unless it is fundamentally changed.

Thus, the plain

meaning of the claim language seeks to describe an impractical,
if not inoperable, circumstance.”

(Defs. Opening Br. at 34.)

The Court has considered the parties’ respective arguments,
the patent claim, the specification and the experts’ testimonial
evidence.

The Court agrees with the patentee that one of

ordinary skill would understand this term to indicate the
material should be destructively tested through differential
78

scanning calorimetry or thermogravimetric analysis.

The Court

also finds that the term “compound of claim 3” does not create
insoluble ambiguity in light of the graph in Figure 2 of the
specification, which shows both differential scanning
calorimetry and thermogravimetric analysis thermograms of the
crystalline monohydrate of the compound of formula (IV).

The

Court thus construes the term “which is further characterized by
a weight loss of 3.48% by thermogravimetric analysis between 50°
C and 175° C” as follows:
“[W]hich is further characterized by a weight loss of 3.48%
by thermogravimetric analysis between 50° C and 175° C, taking
into account variations due to measurement errors and dependent
upon the measurement conditions employed.”

79

IT IS THEREFORE on this

28th

day of March, 2013,

ORDERED that the Court finds:
(1) the term “a compound or salt thereof selected from
the group consisting of” found in claim 6 of United States
Patent No. 6,596,746 (the “‘746 Patent”) is construed as
follows: a compound or its salt (“salt” meaning acidic and/or
basic salts formed with inorganic and/or organic acid and bases)
selected from the claimed list, and
(2) the term “‘N-(2-Chloro-6-methylphenyl)-2-[[6[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4pyrimidinyl]amino-5-thiazolecarboxamide” from the list of
chemical names in claim 6 of the ‘746 Patent is construed
as follows: the compound having the following equivalent
chemical structures

, and
(3) the term “administering to” or “administering
orally to”, found in claims 7, 44, and 47 of the ‘746 Patent, as

80

well as claim 1 of United States Patent No. 7,153,856 (“the ‘856
Patent”) and claims 1, 2, 3, 11, and 27 of United States Patent
No. 7,125,875 (“the ‘875 Patent”), is construed as follows: to
mete out or dispense or to give remedially, and
(4) the term “a subject in need thereof” found in
claims 7, 44, and 47 of the ‘746 Patent, as well as in claim 1
of the ‘856 Patent and in claims 1, 2, 3, 11, and 27 of the ‘875
Patent, is construed as follows: an animal, including a human,
in need thereof, and
(5) the term “wherein the cancer is resistant to
treatment by STI-571”, found in claims 9, 10, 12, and 27 of the
‘875 Patent, is construed as follows: wherein the cancer [or
chronic myelogenous leukemia] exhibits resistance to treatment
by STI-571, and
(6) the term “crystalline monohydrate of the compound

of formula (IV)

”, found in

claims 1, 3, and 12 of United States Patent No. 7,491,725 (“the
‘725 Patent”), is hereby construed as follows: the monohydrate
of the compound of formula (IV) in a crystalline form, and

81

(7) the term “which is characterized by an x-ray
powder diffraction pattern substantially in accordance with that
shown in FIG. 1”, found in claim 1 of the ‘725 Patent, is
construed as follows: which is characterized by an x-ray powder
diffraction pattern that is substantially identical to those
shown in FIG. 1 taking into account variations due to
measurement errors and dependent upon the measurement conditions
employed, but not taking into account the exact order of
intensity of the peaks, and
(8) the term “the compound of claim 1” or “the
compound of claim 3” or “the compound of claim 9” or “the
compound of claim 12”, found in claims

2, 4, 5, 8-11, and 13-16

of the ‘725 Patent, is construed as follows: the monohydrate of
the compound of formula (IV) in a crystalline form, and
(9) the term “a process for preparing the compound of
claim 3”, found in claims 6 and 7 of the ‘725 Patent, is
construed as follows: a process for preparing the crystalline
monohydrate of the compound of formula (IV), and
(10) the terms “[w]hich is characterized by
differential scanning calorimetry thermogram and a
thermogravimetric analysis substantially in accordance with that
shown in FIG. 2”, “[being further] characterized by a
differential scanning calorimetry having a broad peak between
82

approximately 95° C and 130° C”, and “wherein the differential
scanning calorimetry further has a peak at approximately 287°
C”, found in claims 1, 9, 11, and 12 of the ‘725 Patent, are
construed as follows: Which is characterized by differential
scanning calorimetry thermogram and thermogravimetric analysis
patterns that are substantially identical to those shown in FIG.
2, having one peak at approximately 287° C and one broad peak
between approximately 95° c and approximately 130° C; being
further characterized by a differential scanning calorimetry
having a broad peak between about 95° C and about 130° C;
characterized by differential scanning calorimetry with a peak
located at about 287° C which corresponds to the melt of the
dehydrated form of the compound of formula (IV), and
(11) the term “which is characterized by an x-ray
powder diffraction pattern (CuKα λ=1.5418 Å at a temperature of
about 23°C.) comprising four or more 2θ values selected from the
group consisting of 18.0±0.2, 18.4±0.2, 19.2±0.2, 19.6±0.2,
21.2±0.2, 24.5±0.2, 25.9±0.2, and 28.0±0.2”, found in claim 3 of
the ‘725 Patent, is construed as follows: which is characterized
by an x-ray powder diffraction pattern taken with CuKα λ=1.5418 Å
at a temperature of about 23°C, having at least four 2θ values
selected from the group consisting of 18.0±0.2, 18.4±0.2,

83

19.2±0.2, 19.6±0.2, 21.2±0.2, 24.5±0.2, 25.9±0.2, and 28.0±0.2,
and
(12) the term “characterized by unit cell parameters
approximately equal to the following dimensions:
Cell dimensions: a(Å)=13.8632(7); b(Å)=9.3307(3);
c(Å)=38.390(2);
Volume=4965.9(4) Å3
Space group Pbca
Molecules/unit cell 8
Density (calculated) (g/cm3) 1.354”, found in claim 5 of the
‘725 Patent, is construed as follows: characterized by unit cell
parameters approximately equal to the following dimensions:
Cell dimensions: a(Å)=13.8632(7); b(Å)=9.3307(3);
c(Å)=38.390(2);
Volume=4965.9(4) Å3
Space group Pbca
Molecules/unit cell 8
Density (calculated) (g/cm3) 1.354, and
(13) the term “wherein the compound is substantially
pure”, found in claims 8, 15, and 16 of the ‘725 Patent, is
construed to mean: the compound itself having a purity greater
than 90 percent, and

84

(14) the term “which corresponds to the loss of one
water of hydration on thermogravimetric analysis”, found in
claims 9 and 12 of the ‘725 Patent, is construed as follows:
which corresponds to a weight loss attributable to one water of
hydration on thermogravimetric analysis, and
(15) the term “which is further characterized by a
weight loss of 3.48% by thermogravimetric analysis between 50° C
and 175° C”, found in claim 10 of the ‘725 Patent, is construed
as follows: which is further characterized by a weight loss of
3.48% by thermogravimetric analysis between 50° C and 175° C,
taking into account variations due to measurement errors and
dependent upon the measurement conditions employed.

s/ Mary L. Cooper
.
MARY L. COOPER
United States District Judge

85