Free Redacted Document - District Court of Delaware - Delaware

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IN THE UNITED STATES DISTRICT COURT FOR THE DISTRICT OF DELAWAR

GLAXO GROUP LIMITED,
Plaintiff,
v.

Civil Action No. 04-l7l-KAJ

CONFIDENTIAL
FILED UNDER SEAI.J

TEV A PHAR.MACEUTICALS USA, INe. and

TEV A PHARMACEUTICAL INUSTRIS
LIMITED,
Defendants.

TEV A'S OPENING BRIEF IN SUPPORT OF ITS CLAIM CONSTRUCTION
YOUNG CONAWAY STARGATT & TAYLOR, LLP Josy W. Ingersoll (# 1088) Adam W. Poff (# 3990) Karen E. Keller (# 4489) The Brandywine Building 1 000 West Street, 17th Floor P.O. Box 391 Wilmington, DE 19899 Telephone: (302) 571-6600

MERCHANT & GOULD LLC Mark D. Schuman Ronald A. Daignault Jeffer Ali
Jeffrey e. Brown 3200 IDS Center

80 South 8th Street Minneapolis, MN 55402
Teva Pharmaceuticals USA, Iiic. aiid Teva Pharmaceutical Industries, Ltd.

Dated: June 30, 2006

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T ABLE OF CONTENTS
I)age

I. INTRO D U CTI 0 N...... ............ ................. .......... .............. .............. ........ ..... ............1

II. THE LAW OF CLAIM INTERPRETATION .................................................1
III. ETHAN 0 L.. .......................... .......... ........ ...... .... ....... ... .... .......... ... ......... ... ........ .......3

A. Th e In trinsic Evidence..... ................. .......... ...... ...... ....... ........ ............... .....3

1. The '249 Patent Specification .....................................................3
2. Th e Prosecution History................................................................5

B. Th e Extrinsic E viden ce....... ........................... ............. ........... ............... .....8

IV. STABILIZING EFFECTIVE AMOUNT .........................................................11
A. The In trinsic E viden ce...... .......... ............... ....... ..... ............... ............... ....12

B. Th e Extrinsic E viden ce. ............ ..... ............ ............ ..................................15

V. 2.5% TO 10% WEIGHTNOLUME ETHANOL AND 7% TO 8% \VEIGHTNOLUME ETHANOL...............................................16
A. The Intrinsic E viden ce.... ......................... .......... ........... ............ ........... ....17

VI. NO FURTHER ELEMENTS SHOULD BE CONSTRUED ...........................18
VII. CO N CL U SI 0 N ........................................ .................... ............. ................ ...........20

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TABLE OF AUTHORITIES
FEDERAL CASES
Alleii Ellg'g Corp. v. Bartell Indus., Inc., 299 F.3d 1336 (Fed. Cir. 2002)........................19
Amgen Inc. v. Hoechst Marion Roussel, 314 F.3d 1313 (Fed. Cir. 2003) .........................l 0

DeGeorge v. Bemier, 768 F.2d 1318 (Fed. Cir. 1985)......................................................l9
DuPont de Nemours & Co. v. Phillips Petroleum Co" 849 F.2d 1430 (Fed. Cir. 1988), ceiio denied, 488 U.S. 986 (l988) ............................................., 1 0, l8
GlCL\:o V. Pharmadyiie, 32 F. Supp. 2d. 265 (D. Md. 1998)...............................................14

Hoechst Celaiiese COJp. V. BP Chems. Ltd., 78 F.3d 1575 (Fed. Cir. 1996).....................ll
Hogaiias AB V. Dresser Indus., Inc., 9 F.3d 948 (Fed. Cir. 1993).....................................10

KCJCOJp. V. Kineic Concepts, IIlC., 223 FJd l35l (Fed. Cir. 2000)...............................10

Markmaii v. Westview Iiistrumeiits, Inc., 52 F.3d 967 (Fed. Cir. 1995), affd, 517 U.S. 370 (1996)......................................................................................1, 2, 3

Philips V. A WH COJporation, 415 F.3d 1303 (Fed. Cir. 2005).................................2, 3, 1l

Reiisha PLC v. Mmposs Societa per Axioni, 158 F.3d 1243 (Fed Cir.
1998) ........... ............ ............................ ............ .... ........... ......................................, ......, 1 0

SRI Intll v, Matsushita Elec. COJp., 775 F.2d 1107 (Fed. Cir. 1985) ..................................9

u.s. Surgical Co. v, Ethicon, 103 F.3d 1554 (Fed. Cir. 1997) ..........................................19
Tandon COJp. v. lTC, 831 F.2d 1 017 (Fed. Cir. 1987) ......................................................17

Taro Co. V. White Consolo Indus., Ltd., 199 F.3d 1295 (Fed. Cir. 1999) ......................1, l7

Vanderland Indus. Nederland BV v. Intl Trade Comm 'll, 366 F.3d 131 i (Fed. Cir. 2004) .............. ................. ........... ...... .......... ....... .........., '............... ........ ..........1
Vitronics COJp. V. Conceptronic, Inc., 90 F.3d 1576 (Fed. Cir. 1996) ......................2, 3, i 1

FEDERA STATUTES
3S U.S. C. § 112...... ........... ..... ......... ...................................... ............. ................... ...............5

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i. INTRODUCTION
Teva has stipulated that its proposed ANA product satisfies all the limitations of
the claims of Glaxo's '249 patent except the following: "ethanol," "stabilizing effective
amount," "2.5 % to 10% weight/volume ethanol," and "7% to 8% weight/volume

ethanoL." (Exhibit A at M002, June 30,2005 Hearing Trans. p.5)1. Consequently, the
Court need only interpret these four limitations.
Properly construed, ethanol simply means ethanol, "a chemical of

the

nomenclature CH3CHzOH, namely ethanoL." The clause "stabilizing effective amount"

means "an amount of a stabilizer that is suffcient to cause a statistically significant
increase in the time it takes for an aqueous fommlation containing ranitidine
hydrochloride to lose S percent of

the ranitidine present (the "t95" value) as compared to

the same formulation without the stabilizer."
The remaining limitations at issue should be constred to mean precisely how

they read: "2.5% to 1 0% weight/volume ethanol" and "7% to 8% weight/volume ethanol"
respectively.

II. THE LAW OF CLAIM INTERPRETATION
Claim interpretation is a matter of law to be decided by the district court.
Markman v. Westvieìv Iiistrumeiits, Inc., 52 F.3d 967, 970-71 (Fed. Cir. 1995), aff'd, 517

U.S. 370 (1996). The objective of claim construction is to determine what a person of
ordinary skill in the art, having read the written description and prosecution history,

would understand the claims to mean. Vanderlaiid Iiidus. Nederlaiid BV v, Jntl Trade
Comm 'n, 366 F.3d 1311,1318 (Fed. Cir. 2004); Taro Co. v. White Canso!. Indus., Ltd.,

i As used in this brief, references to "Exhibit" are to the Exhbits attached to the Appendix supporting
Teva's Brief in Support of its Claim Constrction.

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199 F.3d 1295, 1299 (Fed. Cir. 1999). "It is a 'bedrock principle' of patent law that the
claims of a patent define the invention to which the patentee is entitled the right to

exclude." Phillps v. A WH Coiporation, 415 F.3d 1303, 1312 (Fed. Cir. 2005) (internal
quotation omitted).

The Federal Circuit recently clarified the proper procedure to follow when
construing the meaning of disputed claim terms. See Philips v. A WH Coiporation, 415

F.3d 1303 (Fed. Cir. 2005) (en banc). In Philips, the Federal Circuit emphasized one
rule above all others - the most important evidence in the construction of claim terms is

that which is intrinsic to the patent. See Phillips, 415 F .3d at 1312; Vitronics Coip. v.

Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996). Intrinsic evidence includes the
claims themselves, the specification, and the prosecution history. Vitronics, 90 F.3d at
1582.

In addition to the words of the claims themselves, the Court should always consult
the written description (or specification) of

the invention. Mar!aiiaii, 52 F.3d at 979. The
415

written description is highly relevant to the claim construction process. Phillps,

F.3d at 1315. Specifically, the person of ordinary skill in the art - whose understanding
of the claim terms is at the heart of the claim construction process - is presumed to have

read the patent in its entirety, including the written description. Id. at 1313. Indeed, the
specification has been deemed "the single best guide to the meaning of a disputed term,"

and serves as the "primary basis" for construing claim terms. Id. at 1315.
Likewise, the prosecution history frequently sheds light on the meaning of claim
terms. Id. at 1317. It often demonstrates the inventor's understanding of

the meaning of

claim terms and the scope of the invention. Id. The prosecution history "can often

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inform the meaning of

the claim language by demonstrating how the inventor understood

the invention and whether the inventor limited the invention in the course of prosecution,

making the claim scope narrower than it would otherwise be," Id. For these reasons,
courts should also consider the prosecution history, if in evidence, when construing claim

terms.- Markman, 52 F.3d at 980.
Of course, a court always is free to consider extrinsic evidence to gain a better
understanding of the background and technical aspects of the invention, so long as such
inquiry is done within the context of

1

the intrinsic record. Philips, 415 F,3d at l317-18.

Extrinsic evidence "consists of all evidence external to the patent and prosecution

history," including dictionaries. Jd. at 1317. Indeed, dictionares are given special
consideration by the courts, as such texts (especially technical dictionaries) "endeavor to collect the accepted meanings of terms used in various fields of science and technology,"

and are generally viewed as unbiased and useful sources in claim construction. Id. (citing
Vitronics, 90 F.3d at 1584, n.6).

III. ETHANOL
The term "ethanol" should be narrowly interpreted to mean "a chemical of the
nomenclature CH3CHzOH, namely ethano1."
A. The Intrinsic Evidence
1. The '249 Patent Specification
The specification of

the patent provides no explicit definition for ethanol, but it

does repeatedly disclose and teach the use of ethanol, and only ethanol, to stabilize

ranitidine oral solutions. Beginnng with the title, the '249 patent informs the public that
, The prosecution history and the '249 patent are attached to the Joint Claim Constrction, as required by the Cour's Second Amended Scheduling Order, dated May 22, 2006. All cites to the intrnsic record in

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it is directed to "AQUEOUS RAITIDIN COMPOSITIONS STABILIZED WITH
ETHANOL." The abstract of

the '249 patent further informs that ranitidine stability is

"enhanced by the addition of ethanoL." ('249 pat. at Abstract) (emphasis added).

Similarly, after identifying several prior art formulations of ranitidine syrup, the '249

patent pronounces that ranitidine oral formulations "may be surprisingly enhanced by the
addition of ethanol

to the fonnulation." (CoL. 1, lines 40-44) (emphasis added).

The '249 patent specification contains no data to indicate how ethanol stabilizes

ranitidine, or how much stabilization is necessary. Instead, the '249 patent specification
states that the amount of ethanol "is such that the resulting formulation has the enhanced

stability." (Col. 1, lines 54-56). The specification then lists differing ranges of the
amount of ethanol, starting at a range of"2.5 to 1 0% W/V,,,3 and decreasing within that

range to an amount deemed "more especially" preferable, "7-8% w/v" of ethanoL. (CoL.

1, lines 56-60). No matter what the amount, ethanol is the sole constituent that is claimed

to enhance the stability ofranitidine. The patent specification discloses only one formula
as an "illustrative example of a formulation according to the invention," and that formula
contains only ethanoL. (CoL. 2, lines 53-65).

The specification, however, makes no effort to define ethanoL. There is certainly

no mention in the '249 patent that ethanol should be defined as an organic compound

"comprising a lower aliphatic hydrocarbon group having two carbon atoms and one OH group," as Glaxo proposes in this litigation.

this brief are to the Exhibits attached to the Joint Claim Statement, 3 The short hand "w/v," as used in the '249 patent, is a reference to "weight/volume." ('249 pat., co!. 1,11.
54-60).

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2. The Prosecution History

Similarly, the file history contains nothing to elucidate the definition of ethanol,

although both the Examiner and Glaxo used the term frequently. Beginning with the first
rejection of Glaxo' s claims, the Examiner concluded that Glaxo' s supposed invention

was not patentable because "the aii teaches the cojoining of ranitidine and an alcohol; e.g. ethanol," and stated that "the addition of a non-critical pH limit and non-critical amounts
(of ethanol) are not seen as patentable limitations to the varioues ( sic) claims."

(G000265)4 (emphasis added). The Examiner also rejected claims 1-10 as indefinite

under 35 U.S.e. § 112, second paragraph, and claims 1-l2 under 35 U.S.e. § ll2, first
paragraph. (G000264). Glaxo responded with an Amendment dated November 7,1988.
(G000267-270). The Examiner again rejected all of

the claims on November 29,1988.

(G000271-272). Glaxo then abandoned its first application and filed a continuation
application on April 28, 1989, which was given Serial No. 07/344,620.
On June 28,1989, the Examiner once again rejected all of

the claims. (G000130-

135). Glaxo responded on October 30, 1989, by amending its claims to state that the
claimed invention is to include a "stabilizing effective amount of' ethanoL. (G000139)

(emphasis added). Glaxo included this claim amendment to "functionally" define "the
amount of ethanol present." (GOOO 140) (emphasis added). Glaxo also argued that the

prior art cited by the Examiner in the first rejection did not teach one of skill in the art "to
expect that the stability of ranitidine in an aqueous oral formulation could be enhanced by

the presence of ethanol and does not suggest a presence of ethanol in such compositions."
(GOOO 141-142) (emphasis added). Glaxo continued by arguing that the only fair

4 File history documents, referenced herein as "0000111 though 0000308" are attached as Exhibits 2 and
3 to the Joint Claim Constrction Statement fied contemporaneously with this brief.

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inference fTom the prior art references "is that ranitidine hydrochloride must be

reasonably stable in ethanol since ethanol is used as a solvent for recrystallization,"
(G000142) (emphasis added).

On November l4, 1989, the Examiner again rejected the amended claims, noting
that the "art clearly precludes applicants claims to ranitidine and ETOH."s (GOOO 161)

enhanced
(emphasis added). The Examiner also noted, "(a)s for the allegation of

stability, it has not been demonstrated for the compositions urged as contrasted with any

of other pH parameters." Id. The Examiner made the November 14, 1989, rejection
finaL. (G000162). Glaxo responded by abandoning that application and fiing a separate

continuation application. (G000164-166). On May 4,1990, the Examiner again rejected
all claims of

the application for the identical reasons set forth in the June 28,1989, Office

Action. (G000169-17l).

Glaxo responded with another amendment on October 31, 1990. Glaxo argued
that one of ordinary skill would not be lead by the prior art to "in any way expect the
stability ofranitidine in an aqueous oral fODnulation could be enhanced by the presence

of ethanol and does not suggest the presence of ethanol in such compositions."
(GOOOl75) (emphasis added).

The Examiner again rej ected Glaxo' s claims, citing new prior art that had been

disclosed by Glaxo. (G000198-201). The Examiner also challenged Glaxo to
demonstrate, through experimental data, that its purported invention - the use of ethanol

in the formulation - produced "any unexpected results," showing "a definite

improvement over" Glaxo's prior patent. (G000200). The Examiner noted that because
5 "ETOH" is chemical shortand for "ethanol." 17le Hawley's Condensed Chemical Dictional)', iith
Edition (1987), p. 477 (Exhbit B at MOOS).

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a prior Glaxo patent taught "an aqueous composition ofranitidine, it is considered well
within the state of the art to choose ethanol as an additive which would be considered

pharmaceutically acceptable when formulating this composition." Id. (emphasis added).
On May 10,1991, Glaxo requested reconsideration of

the Examiner's rejection,

this time arguing that "there is a clear disincentive against the use of ethanol in aqueous formulations" because ranitidine is used to treat peptic ulcers and related conditions that

can be aggravated by "alcohol (i.e., ethanol)." (G000206) (emphasis added). Glaxo
argued that "onlv by the present invention," would one of ordinary skill in the art

recognize the stabilizing benefits of ethanol in the formulation. Id. (emphasis added).
In further support of Glaxo's claim to the unique and specific benefits of ethanol

to stabilize ranitidine, Glaxo submitted the Declaration of one of its scientists, Dr. John

HempenstalL. (G000208-211). Dr. Hempenstalls declaration purported to provide the
experimental data the patent Examiner had sought since the November 14, 1989 rejection.

Dr. Hempenstall, who at the time was "a Research Leader" in the Pharmacy Division of
Glaxo, declared that ethanol, in Glaxo' s ranitidine formulation, resulted in a "surprising
eimancement in the stability of

the ranitidine...." (G000209). The Examiner then

allowed all of

the pending claims. (G000212-214).

In summary, both the Examiner and the applicant discussed ethanol in terms of
the prior art throughout the prosecution of

the patent. Not once did Glaxo contend that

the tern1 "ethanol" should be given any special meaning. Indeed, throughout the
prosecution, both Glaxo and the Exan1iner assumed that ethanol meant ethanoL. Even

when Glaxo deviated from describing ethanol, it used the term "alcohol," the common
synonym of ethanoL. It did not use the phrase "an organic compound comprising a lower

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aliphatic hydrocarbon group having two carbons and one -OH group" even once

throughout the entirety of the prosecution of the patent. The only question, then, is what
one of ordinary skill understands ethanol to mean.
B. The Extrinsic Evidence

Webster's New Collegiate Dictionary defines ethanol by directing the reader to
the definition of

"alcohoL." Alcohol is defined as "a colorless volatile flammable liquid

CzH60 that is the intoxicating agent in fermented and distilled liquors and is used also as

a solvent - called also ethyl alcohoL" (Exhibit Cat M09-MOI0). The Hawley's
Condensed Chemical Dictionary, 11th edition, (the same edition relied upon by Glaxo's

expert, Dr. Anderson) defines "ethanol" by directing the reader to the definition of "ethyl
alcohol," which is defined as "alcohol; grain alcohol, ethanol; EtOH," and "C2HsOH.,,6

(Exhibit B at M 005). Even the "Handbook of Chemistry and Physics" text, another
treatise selected by Glaxo's expert, defines "ethanol" simply as "alcohoL. Ethyl alcohoL.
Methyl carbinoL. C2HsOH." (Exhibit D at MOI4). Each of

these references has in

common the simple use of a chemical formula to identify and define ethanoL.

Reduced to its essence, ethanol has its most unambiguous definition in its

chemical formula, CH3CH20H. The public (including Teva) is justified in relying on
Glaxo's unequivocal, unambiguous, and repeated statements to the Patent Office that the
use of

"ethanol" was Glaxo's invention.

Glaxo does not appear to dispute the fact that the intrinsic evidence does not

define ethanol in any unique or special manner. Yet, Glaxo's definition adds "an organc

6 Note that three of these term, "ethanol," "alcohol," and "EtOH" were all used by either the Examiner or
Glaxo interchangeably thoughout the prosecution of

the '249 patent. (G000265) (Examiner uses "alcohol;

e.g. ethanol"); (GOOOI61) (Examiner uses "Etoh" to refer to ethanol); (G000206) (Glaxo uses "alcohol (i.e. ethanol")).

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compound comprising a lower aliphatic hydrocarbon group having two carbon atoms and
one -OH group," among other extraneous language, to the chemical formula of ethanoL.

Glaxo seeks to characterize ethanol in such a manner so that it can bootstrap its
infringement argument into the definition of "ethanoL." Teva does not use ethanol in its

formulation, so there can be no literal infrngement no matter how ethanol is interpreted.
T eva uses.

~eÒ-ac\e

Ò

, according to Glaxo' s expert, is

(Exhibit E at
M021, Anderson 3/16/06 Expert Report, '1 74).

Glaxo hopes to use its definition as a springboard for its argument that Teva
infrnges under the doctrine of

equivalents. Indeed, Glaxo's motivation for its

construction is transparently betrayed by its own expert, Dr. Anderson, who mimics most
of Glaxo' s proposed definition of ethanol word for word when describing

Redacted

l, a wholly different chemical compound. (Exhibit E at MO 17 - MO 18, Anderson

3/16/06 Report at ~ 34) (noting his opinion that the '249 covers the use of ethanol.

c\eÒ ~eÒ~
Glaxo's proposed construction violates the rules of

claim construction. It is

settled law that claims must not be construed with reference to an accused product. See
SRI Int 'I v. Matsushita Elec. C01P" 775 F.2d 1107, 1118 (Fed. Cir. 1985) ("It is only

after the claims have been construed without reference to the accused device that the

claims, as so construed, are applied to the accused device to determine infrngement.").
Glaxo's construction is a semantics exercise, seeking to make the term "ethanol" look as
much as possible like

Redacted

as used by Teva in the accused formulation.

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By using words like "comprising" and "a" in its proposed claim construction,
Glaxo also hopes to expand the definition of ethanol to any lower, aliphatic organic
compound with at least two carbon atoms and one -OH group. See Amgen Inc. v.

Hoechst Marion Roussel, 314 F.3d 1313, 1344-45 (Fed. Cir. 2003) ("Comprising is a
term of art used in claim language which means that the named elements are essential,
but other elements may be added and still form a construct within the scope of

the

claim."); KCJ COJp. v. Kineic Concepts, Inc., 223 F.3d 1351, 1356 (Fed. Cir. 2000) (An

indefinite article' a' in patent parlance carres the meaning of one or more in open-ended
claims containing the transitional phrase comprising.). However, adopting Glaxo's

proposed construction brings just about every other alcohol and non-alcohol compound

with at least two carbon atoms and one -OH group within the scope of the claims. There
is no intrinsic or extrinsic support for such a broad construction of such an unambiguous word like "ethanoL." Consequently, Glaxo's proposed construction should be rejected.

Further, district courts are consistently cautioned by the Federal Circuit to be
careful not to import undue limitations into the definitions of claim terms when they are

not necessary. See Rensha PLC v. Marposs Societa per Axioni, 158 F.3d 1243, 1248
(Fed Cir. 1998) ("If we need not rely on a limitation to interpret what the patentee meant
by a particular tem1 or phrase in a claim, that limitation is 'extraneous' and cannot
constrain the claim.") (citations omitted); see also Hoganas AB v. Dresser Indus., fIiC., 9

F.3d 948, 950 (Fed. Cir. 1993) ("It is improper for a court to add 'extraneous' limitations

to a claim, that is, limitations added wholly apar from any need to interpret what the
patentee meant by particular words or phrases in the claim.") (quoting Du Pont de

Nemours & Co. v. Phillps Petroleum Co., 849 F.2d 1430, 1433 (Fed. Cir. 1988)). The

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extraneous language proposed by Glaxo is not necessary to define the common
understanding of the term "ethanoL." Indeed, no less than three dictionaries use ethanol's chemical formula as a common definition for ethanoL. Glaxo's proposed construction
should therefore be rejected.

The Federal Circuit directs courts to give claim terms their ordinary meaning
absent an express intent by the inventor to impart a different meaning to the terms at

issue. Phillips, 415 F.3d at 13l2-13 (citing, among other cases, Vitrionics Coip. v.
Conceptronic. Inc., 90 F.3d 1576, l582 (Fed. Cir. 1996)). Further, if

the word is a

technical term, it "is interpreted as having the meaning that it would be given by persons experienced in the field of the invention, unless it is apparent from the patent and the

prosecution history that the inventor used the term with a different meaning." Hoechst

Celanese Corp. v. BP Chems. Ltd., 78 F.3d 1575, 1578 (Fed. Cir. 1996). Here, there is
no indication in the intrinsic evidence that the term ethanol was meant to refer to
anything but the chemical compound commonly understood as ethanoL. Therefore, the

Court should not look beyond the plain and ordinary meaning of the word "ethanol" to
construe it as "a chemical nomenclature of CH3CHzOH, namely ethanoL." No further

description is necessary to fully and completely define the term "ethanol" to those skilled
in the art.

iv. STABILIZING EFFECTIVE AMOUNT
The tenn "stabilizing effective amount" is properly construed to mean "an amount

of a stabilizer that is sufficient to cause a statistically signficant increase in the time it
takes for an aqueous fommlation containing ranitidine hydrochloride to lose 5 percent of
the ranitidine present (the "t95" value) as compared to the same formulation without the

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stabilizer." Glaxo provides this definition in the prosecution history of

the '249 patent

through the experimental evidence it supplied to the Examiner and upon which the

Examiner relied. The declaration gave a methodology for determining whether the added

stabilizer substantially enhanced the stability ofranitidine solution. Glaxo is bound by
this methodology - the only indication in the patent or fie history of

what "a stabilizing

effective amount" means.
A. The Intrinsic Evidence

The '249 patent does not explicitly define what "a stabilizing effective amount"
means. It does, however, state that the invention is directed to substantial stability

enhancement:

We have now surprisingly found that the stability of ranitidine in aqueous based formulations and more particularly aqueous based formulations for oral administration may be substantially enhanced by the addition of
ethanol to the formulation.

(Co!. 1, lines 40-44) (emphasis added). The '249 patent does not, however, offer a
specific definition of the clause "a stabilizing effective amount."
Throughout most of

the file history, the applicants and Examiner also did not

define what "a stabilizing effective amount" meant. The Examiner did, however, initially
reject Glaxo's claims as indefinite, to which Glaxo responded with its first amendment

adding "stabilizing effective amount" to claim 1. (G000139). Glaxo described its
amendment as an effort to "functionally definer)" the amount of ethanol present in the

formulation. (G000140). The Examiner accepted the amendment at face value, but
nonetheless rejected the claims as unpatentable. (G000198-20 1). The Examiner noted
that because Glaxo' s prior ranitidine patent "teaches an aqueous composition of
ranitidine, it is considered well within the state of

the art to choose ethanol as an additive

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which would be considered pharmaceutically acceptable when formulating this

composition." (G000200). The Examiner then asked for evidence from Glaxo showing
that the addition of ethanol was more than just "a choice among known conventional
excipients." Id.

Glaxo ultimately responded to the Examiner's request for data by submitting a
declaration from one of its scientists, Dr HempenstalL. (G000208-21 1). In that

declaration, Mr. Hempenstall, a Glaxo scientist with a doctorate in Pharmaceutical

Sciences from the University of Aston in Binningham, summarized to the Patent Office
an analysis of data performed by others at Glaxo and argued the data showed substantial
enhancement. (G000209). Dr. Hempenstall declared "(tJhe advantageous effect resulting

from the addition of ethanol to an aqueous based ranitidine formulation can readily be
determined by comparing the stabilitv of

the ranitidine in a formulation according to the

present invention and the same formulation but without the ethanol added." Id. at ~ 5
(emphasis added).
To make this comparison, Dr. Hempenstall first recognized that "acceptable shelf

life for an aqueous formulation containing ranitidine hydrochloride is considered to be

the time at which no ~ than 5% of the ranitidine present in the formulation has
degraded."? (G000210 at ~ 6) (emphasis added). Dr. Hempenstall's t95 results were

"calculated at the lower 95% confidence limit." (G00021 0). A "confidence limit" is well

known as a statistical analysis of data. See Reference Manual of Scientifc Evidence 376
(1994) (a confidence interval is derived using a particular model of statistical error), Dr.
Hempenstall, in his declaration, then compared the t95 values for solutions containing

ethanol to solutions not containing ethanoL. (G000209 at,1 5). Dr. Hempenstall observed

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that an increase in shelf life of six months occurred at 30DC, an increase he deemed "a

highly significant and valuable improvement." (G000211 at'1 6, p. 4) (emphasis added).
Dr. Hempenstall, in a prior litigation, testified that Glaxo performed a statistical analysis

on the data to determine its significance before submitting his declaration to the Patent

Offce. Glaxo v. Pharmadyne, 32 F. Supp. 2d. 265, 311 (D. Md. 1998) (noting that
"Before Dr. Hempenstall prepared his declaration he asked for statistical analyses of the

comparative studies that Glaxo had conducted on ethanol and non-ethanol solutions" partly because his predecessor questioned "whether the ethanol stability effect was
si gnificant.") (emphasis added).

In sum, Dr. Hempenstalls declaration establishes the following methodology for

the term "stabilizing effective amount"
l. The 12i value for a solution containing the stabilizer must be measured;

2. The t95 value for a solution devoid of

the stabilizer must be measured; and

3. The 12i value for the stabilized solution must be compared with the t95_

value for the unstabilized solution and the increase in 12i time due to the stabilizer must be statisticallv significant.

Dr. Hempenstall ultimately concluded that his data showed that "a significant and
surprising enhancement in the stability of

the ranitidine is achieved by the addition of

ethanoL" (G000209 at ii 5) (emphasis added). Thus, the intrinsic record teaches that to
know whether any amount of excipient added to a ranitidine solution produces a
substantial enhancement of

the solution, a statistical comparson between the t95 values

for the same solution both with and without the stabilizing component must be made.

7 This is also known as the t95 value. (Exhbit A at M019-M020, Anderson 3/16/06 Report at ~ 44.)

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B. The Extrinsic Evidence

Glaxo agrees that the time at which 5% ranitidine degradation occurs is

commonly understood as (Exhibit E at MOI9-M020, Anderson Report at
'144 (stating

Redacted

Redacted

). Further, Glaxo's expert correctly observes that the t95 value

Redacted

Id.

Importantly, Glaxo's expert also agrees that the term "substantially enhanced" as used in
the '249 patent,

Redacted
.." (Exhibit F at M024,

Anderson, April

24, 2006 Rebuttal Report, ~ 27.) In fact, Glaxo's expert unequivocally

agrees that Dr. Hempensta1ls declaration, submitted to the Patent Office during
prosecution, demonstrated to the Patent Office a statistically significant enhancement of
the stability of ranitidine:

Redacted

¡d.

The proper construction, therefore, of "a stabilizing effective amount" is one that
identifies what a substantial increase in shelf life means, and further acknowledges how

to detern1ine that increase. Just as Dr. Hempenstall demonstrated to the Patent Office, "a stabilizing effective amount" is properly construed to mean "an amount of a stabilizer
that is suffcient to cause a statistically significant increase in the time it takes for an

aqueous formulation containing ranitidine hydrochloride to lose 5 percent of

the

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ranitidine present (the "t95" value) as compared to the same formulation without the
stabilizer. "

Glaxo's definition ignores the fact that to get its patent, it had to submit the tests

and results run by Dr. Hempenstall. Only then did the Examiner allow the claims. Dr.
Hempenstalls methodology must therefore define the functional term "stabilizing

effective amount." Glaxo's definition is merely a circular exercise in redundancy,
providing no link to the critical data that Glaxo submitted to the Patent Office.

V. 2.5% TO 10% WEIGHTNOLUME ETHANOL AND 7% TO 8% WEIGHTNOLUME ETHANOL
The proper construction of"2.5% to 10% weight/volume ethanol" and "7% to 8%

weight/volume ethanol," appearing in claims 2,3, 11, and 12 respectively, are simply
"2.5% to 10% weight/volume ethanol" and "7% to 8% weight/volume ethanoL." This

Court should not construe these terms beyond their normal and customary meaning. Both
limitations are clear and unmistakable in that they define various numerical ranges of the

amount of ethanol to be used in the claimed fornmlations, calculated as a percentage of
the weight compared to the volume of the total formulation. None of

these claims

include the limitation that the stated ranges for the amount of ethanol have a "stabilizing

effect" on the ranitidine solution-which is what Glaxo urges--except to the extent that
such a limitation is imposed upon claims 2 and 3 by virte of

the separate limitation in

the independent claim 1 from which they depend. There is no need to import any further
limitations into any of these tern1S. Indeed, when Glaxo amended claim 1 to include "a

stabilizing effective amount" of ethanol, it could have also amended the claims 2, 3, 11

and 12 in the same manner, but it did not. The law presumes that Glaxo meant to
maintain a difference between claim 1 and the other claims with numerical ranges when it

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had the opportunity to add the "stabilizing effective amount" language to the numerical

range claims, but did not. See Toro Co. v. White CO/lol. Indus., Inc., 199 F.3d 1295
(Fed. Cir. 1999) ("There is presumed to be a difference in meaning and scope when
different words and phrases are used in separate claims.") (citing Tandoii COlp. v. lTC,
831 F.2d 1017, 1023 (Fed. Cir. 1987).
A. The Intrinsic Evidence

Claims 2 and 3 both recite the pharmaceutical composition of claim 1 with an added limitation that identifies specific ranges for the amount of ethanol to use in the

formulation. (Co!. 3, lines 5-7; 8-10). Claim 2 identifies "2.5% to 10% weight/volume
ethanoL" Claim 3 states a narrower range, "7% to 8% weight/volume ethanoL." Id. Both
claims identify the amount of ethanol as an amount "based on the complete formulation."

Id. Claim 11 is an independent claim that also more specifically defines the amount of
ethanol, "7% to 8% weight/volume ethanol." Id. at 4: 10-16.
The '249 specification provides ample confirmation that both range limitations

mean precisely what they say:

The amount of ethanol in the formulation for oral administration, expressed as a percentage of the complete formulation on a weight/volume basis, is preferably within the range 2.5 to 10%, and more particularly
between 5 to 10%, more especially 7-8%.

(Cot. 2, lines 30-34). The specification identifies each claimed range as the "preferred"
and "more particularly preferred" ranges for the amount of ethanol to use in the claimed
formulations, and concludes with an example of a complete recipe of one formulation,

using 7.5% weight/volume based on the complete formulation. (CoL. 2, lines 53-64). No
further construction is necessary to fully understand that the numerical ranges claimed in
claims 2,3, 11 and 12. They mean simply what they say.

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The prosecution history reveals no effort by Glaxo to impart any unique definition

to the ranges for the amount of ethanol included in claims 2, 3, 11 or 12. In fact, the
claims that recited specific ranges for the amount of ethanol to use in the formulations
survived through prosecution without amendment. (Compare col. 3, lines 5-8 to
G000120) (reciting identical

language for claim 2). More particularly, while Glaxo

amended the originally fied claim 1 in order to "functionally define" that claim, it did not
so amend claims 2, 3, 11, or 12. Glaxo had the oppoiiunity to amend its claim language in these claims during prosecution, but it did not. It is not for this Court to add
limitations that G1axo, itself, apparently chose not to add during prosecution.
As issued, claims 2, 3, 11 and 12 recite a forn1Ulation ofranitidine with specific

ranges for the amount of ethanoL. None of the issued claims address whether the amount

of ethanol so specified is "a stabilizing effective amount," or not. The law does not allow
extraneous limitations to be read into claim limitations. DuPont de Nemours & Co. v.

Philips Petroleum Co., 849 F.2d 1430, 1433-34 (Fed. Cir. 1988), cert. denied, 488 U.S.
986 (1988). Glaxo's proposed construction reads a limitation into the ranges found in

claims 2,3, 11 and 12 that is not necessary, and was not inserted by Glaxo during
prosecution. Glaxo' s definition should be rejected.

VI. NO FURTHER ELEMENTS SHOULD BE CONSTRUED
Glaxo proposes a construction of

"aqueous formulation for oral administration,"

found in claims 1 - 1 0, and "aqueous formulation of ranitidine suitable for oral
administration," found in claims 11 and 12. Both of

these phrases need not be construed,

however, because Teva has stipulated that its proposed ranitidine formulation meets these

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phrases.8 The Federal Circuit has been clear that a district court need not (and should

not) repeat or restate every claim term when construing patent claims. u.s. Surgical Co.
V. EthicOIl, 103 F.3d 1554, 1568 (Fed. Cir. 1997). To the contrary, "(cJlaim construction

is a matter of resolution of disputed meanings and technical scope," focused on

clarifying, only when necessary, what the patentee's claims are. Id. (emphasis added).
The claim construction of the phrases proposed by Glaxo pertaining to "aqueous"
formulations are not at issue in this case, and should not be construed.

8 The phrases are in the "preamble" to each of

the claims. Under Federal Circuit precedent, a claim's preamble generally does not serve as a limitation of a patent claim. Rather, a preamble merely establishes
the background or context for the patent claim. Allen Eng 'g Co/po v. Bartell Indus., Inc., 299 F.3d 1336,

1346 (Fed. Cir. 2002) ("Generally, the preamble does not limit the claim."); accord DeGeorge v. Bernier,
768 F.2d 1318, 1322 n.3 (Fed. Cir. 1985).

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VII. CONCLUSION
For the reasons stated above, Teva respectfully urges the Court to adopt its
proposed constructions of the disputed claim tern1S presented for construction.

YOUNG CONAWAY STARGATT & TAYLOR, LLP

Adam W. Poff (# 3990) Karen E. Keller (# 4489) The Brandywine Building 1000 West Street, 17th Floor
P.O. Box 391

JOSY~88)

Wilmington, DE 19899 Telephone: (302) 571-6600

MERCHANT & GOULD LLC Mark D. Schuman Ronald A. Daignault
J effer Ali Jeffrey C. Brown

3200 IDS Center 80 South 8th Street Minneapolis, MN 55402
Teva Pharmaceuticals USA, Inc. and Teva Pharmaceutical Industries, Lid.

Dated: June 30, 2006

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CERTIFICATE OF SERVICE

I, Adam W. Poff, Esquire, hereby certify that on June 30, 2006, I caused to be
electronically fied a true and correct copy of the foregoing document with the Clerk of the Court

using CM/ECF, which will send notification that such filing is available for viewing and
downloading to the following counsel of record:

Francis DiGiovani Esquire Connolly Bove Lodge & Hutz LLP The Nemours Building
1007 North Orange Street Wilmington, DE 19801
I further certify that on June 30, 2006, I caused a copy of

the foregoing document to be

served by hand delivery on the above-listed counsel of

record and on the following non-

registered participants in the manner indicated:

BY FEDERAL EXPRESS
Brian P. Murphy, Esquire
Thomas Puppa, Esquire

Morgan Lewis & Bockius, LLP
101 Park A venue

New York, NY 10178-0060

YOUNG CO~GATT & TAYLOR, LLP

Adam W. Poff (No. 3990) The Brandywine Building 1 000 West Street, 17th Floor
Wilmington, Delaware 19801

(302) 571-6600 apoff(fycst.com
Attorneys for Teva Pharmaceuticals USA, Inc. and Teva Pharmaceutical Indusstries, Ltd.

DBD 1 :1593524.1

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