Court Opinion

ID: 868379
Source: CourtListenerOpinion
Date Created: 2013-05-21 00:01:22.382948+00
Date Added: 2024-06-11T15:27:03.574173
License: Public Domain

United States Court of Appeals
     for the Federal Circuit
     AVENTIS PHARMACEUTICALS INC.,
             Plaintiff-Appellant,

                       AND

          AMR TECHNOLOGY, INC.,
  (now known as Albany Molecular Research, Inc.),
               Plaintiff-Appellant,

                        v.

AMINO CHEMICALS LTD., DIPHARMA FRANCIS,
        SR.L., AND DIPHARMA SPA,
            Defendants-Appellees,

                       AND

      MYLAN PHARMACEUTICALS INC.,
               Defendant.

             -------------------

     AVENTIS PHARMACEUTICALS INC.,
             Plaintiff-Appellant,

                       AND

          AMR TECHNOLOGY, INC.,
  (now known as Albany Molecular Research, Inc.),
               Plaintiff-Appellant,

                        v.
AVENTIS PHARMA   v. MYLAN PHARMA                        2

       TEVA PHARMACEUTICALS USA, INC.,
                 Defendants,

                           AND

AMINO CHEMICALS LTD., DIPHARMA FRANCIS,
        SR.L., AND DIPHARMA SPA,
            Defendants-Appellees.

                  ______________________

                     2011-1335,-1336
                  ______________________

    Appeals from the United States District Court for the
District of New Jersey in Nos. 04-CV-1077, and 04-CV-
1078, Chief Judge Garrett E. Brown Jr.
              ___________________________

                  Decided: May 20, 2013
              ___________________________

    PAUL H. BERGHOFF, McDonnell Boehnen Hulbert &
Berghoff LLP, of Chicago, Illinois, argued for plaintiffs-
appellants, Aventis Pharmaceuticals Inc. and AMR Tech-
nology, Inc. With him on the brief were JAMES C. GUMINA,
JEREMY E. NOE and PAULA S. FRITSCH. Of counsel on the
brief were LIZA M. WALSH, Connell Foley LLP, of Rose-
land, New Jersey; ANDREW P. ZAPPIA, RICHARD A.
MCGUIRK, WENDELL W. HARRIS, TATE T. TISCHNER and
SHELLEY A. JONES, Leclairryan, Rochester, New York.

    ANTHONY W. SHAW, Arent Fox LLP, of Washington,
DC, argued for defendants-appellees, Amino Chemicals
Ltd., et al. Of counsel on the brief was JOERG-UWE SZIPL,
Griffin & Szipl PC, of Arlington, Virginia.
3                          AVENTIS PHARMA   v. MYLAN PHARMA

                __________________________

    Before NEWMAN, BRYSON, * and REYNA, Circuit Judges.
     Opinion for the court filed by Circuit Judge REYNA.

      Dissenting opinion filed by Circuit Judge BRYSON.

REYNA, Circuit Judge.

     Aventis Pharmaceuticals, Inc. and Albany Molecular
Research, Inc. (AMRI) (collectively “Appellants”) appeal a
stipulated judgment of noninfringement entered by the
U.S. District Court for the District of New Jersey. The
parties stipulated to noninfringement following the dis-
trict court’s Markman opinion of January 13, 2011, which
consolidated numerous patent infringement cases and
construed terms of AMRI’s U.S. Patent No. 5,750,703
(“the ’703 patent”), among others. 1 Because we conclude

     * Circuit Judge Bryson assumed senior status on
January 7, 2013.

     1  Two cases were originally before this court,
though they were both appealed from the same Markman
Opinion and Order of January 13, 2011. The first case,
Albany Molecular Research, Inc. v. Dr. Reddy’s Labs, Ltd.,
No. 2011-1232, was heard by the above panel on Decem-
ber 5, 2011, and relates to the district court’s claim con-
struction of U.S. Patent No. 7,390,906. The second case,
Aventis Pharmaceuticals, Inc. v. Dr. Reddy’s Labs, Inc.,
No. 2011-1334, -1335, -1336, was heard by the same panel
on March 15, 2012, and relates to the district court’s
claim construction of the ’703 patent. Subsequent to the
March 15 oral argument, Dr. Reddy’s Labs and AMRI
engaged in protracted settlement negotiations, finally
culminating in settlement of all pending matters involv-
AVENTIS PHARMA   v. MYLAN PHARMA                         4

that the district court’s Markman opinion misinterpreted
claim terms of the ’703 patent, we reverse and remand.

                     I.   BACKGROUND

    This case concerns the processes used to make various
piperidine derivatives, which are commonly used as active
ingredients in antihistamines. Dr. Thomas E. D’Ambra,
AMRI’s president, found the prior art processes for mak-
ing piperidine derivatives inefficient. Because one goal of
Dr. D’Ambra’s work was to obtain substantially pure
piperidine derivative compounds—ultimately required for
pharmaceutical-grade end products; that is, end products
with greater than 98% purity—he recognized that the
reduced purity achieved through known teachings meant
additional purification steps were required after the
piperidine derivative was fully formed, leading to low
yields. The prior art processes, in short, were costly and
time consuming.

    Dr. D’Ambra’s invention overcame the deficiencies in
the prior art by synthesizing piperidine derivatives using
piperidine and cyclopropylketone (“CPK”) intermediates
at an earlier stage in the reaction. The processes devel-
oped by Dr. D’Ambra have the stated advantage of more
readily separating out a substantially pure piperidine
derivative end product, if desired. Dr. D’Ambra claimed
these novel methods in his ’703 patent. 2 Fexofenadine, a

ing Dr. Reddy’s on February 4, 2013. The settlement
terminated the 2011-1232 and -1334 appeals. Only the
2011-1335 and -1336 appeals remain pending before this
court.

   2   The application for the ’703 patent, U.S. Patent
Application No. 382,649, was filed on Feb. 2, 1995. The
’703 patent, entitled “Piperidine Derivatives and Process
5                           AVENTIS PHARMA   v. MYLAN PHARMA

specific piperidine derivative, can be synthesized using
these methods. See ’703 patent col. 26 ll. 17–33 (claim 7).

    Dr. D’Ambra eventually assigned the ’703 patent to
AMRI. 3 Sanofi-Aventis U.S., the exclusive licensee, uses
the patented processes to produce large quantities of
fexofenadine, which is the active ingredient in its antihis-
tamines marketed under the brand name Allegra® and
Allegra-D® 24 Hour. The issues relevant to this appeal
gravitate around claims 1, 6, and 7 of the ’703 patent.

                   A. Technical Background

           1. Independent Claim 1 of the ’703 Patent

              a. The Patented Process Generally

    As its title suggests, the ’703 patent describes pro-
cesses for synthesizing piperidine derivatives. See supra
note 2. Claim 1 of the ’703, the only independent claim in
suit, describes a process of preparing a piperidine deriva-
tive using a CPK intermediate and a piperidine interme-
diate. The structure of the piperidine derivative to be
prepared as an end product is provided in claim 1 of the
’703 patent as:

for Their Production,” issued on May 12, 1998. The ’703
patent is a divisional of U.S. Patent Application No.
08/083,102 (“the ’102 application”), which was filed on
June 24, 1993.
       3   AMRI was formerly known as AMR Technology,
Inc.
AVENTIS PHARMA   v. MYLAN PHARMA                          6

’703 patent col. 23 ll. 47–61. In the above depiction, R1 is
a hydrogen or hydroxyl group, R2 is a hydrogen group, 4 R3
is a –COOH (carboxylic acid) or –COOR4 (carboxylic acid
ester) group, and R4 is a hydrocarbon chain with one-to-
six carbon atoms.

    The patented process of claim 1 generally involves the
reaction of a piperidine compound like this

with a CPK intermediate of the general structure

    4  Alternatively, R1 and R2 can form a double bond
between the carbon atoms bearing R1 and R2.
7                           AVENTIS PHARMA   v. MYLAN PHARMA

                                             ,
where A, R1, R2, and R3 are defined as described for the
piperidine derivative product. See, e.g., ’703 patent col. 24
ll. 10–17, 22–34.

    The CPK intermediate exists in one of two predomi-
nant regioisomeric states: 5 either para-CPK or meta-
CPK. 6 The para-CPK intermediate regioisomer has the
two aromatic ring substituents located on carbons 1 and
4, on directly opposite sides of the aromatic ring. The
meta-CPK intermediate regioisomer has the two aromatic
ring substituents located on carbons 1 and 3, in a non-
linear orientation. The different regioisomeric forms are
depicted below.

    5   Regioisomers are chemical compounds with the
same molecular formula, but with different bonding
orders.

    6     The CPK intermediate can also exist in an ortho-
structure, with the aromatic ring substituents adjacent to
each other. However, ortho-CPK is rarely produced and
of little biological efficacy, so it is ignored for the remain-
der of this discussion.
AVENTIS PHARMA   v. MYLAN PHARMA                          8

     The difference between these regioisomeric arrange-
ments of constituents on both the CPK intermediate and
piperidine derivative product appears slight, but is biolog-
ically significant—the piperidine derivative produced
using the para-CPK structure is biologically active, while
the piperidine derivative produced using the meta-CPK
structure is biologically inactive. The ’703 patent exten-
sively criticizes the prior art processes because each stage
of the synthesis yields an impure mixture of meta- and
para-regioisomers. But the new process invented by Dr.
D’Ambra using a CPK intermediate means that the
para/meta CPK regioisomeric mixture is more readily
separable to obtain para-CPK, resulting in a substantially
pure para-piperidine derivative end product.

                 b. “Substantially Pure”

   Claim 1 of the ’703 patent reads in its entirety:

   1. A process of preparing a piperidine derivative
   compound of the formula:
9                        AVENTIS PHARMA   v. MYLAN PHARMA

    wherein

       R1 is hydrogen or hydroxyl;

       R2 is hydrogen;

    or R1 and R2 taken together form a second bond
    between the carbon atoms bearing R1 and R2;

       R3 is –COOH or –COOR4;

       R4 has 1 to 6 carbon atoms;

       A, B, and D are the substituents of their
       aromatic rings, each of which may be dif-
       ferent or the same, and are selected from
       the group consisting of hydrogen, halo-
       gens, alkyl, hydroxyl, alkoxy, or other sub-
       stituents,

    said process comprising;

       providing a substantially pure regioisomer
       of the following formula:
AVENTIS PHARMA   v. MYLAN PHARMA                           10

        converting the substantially pure regioi-
        somer to the piperidine derivative com-
        pound with a piperidine compound of the
        formula:

’703 patent col. 23 l. 45 to col. 24 l. 35 (claim 1) (emphases
added). There are two notable features of claim 1 of the
’703 patent. First, the piperidine derivative end product
synthesized through the claimed process covers a broad
range of potential piperidine derivatives as components A,
B, and D—substituents of the aromatic rings—that can be
selected from groups such as hydrogen, halogens, alkyl,
hydroxyl, alkoxy or other groups. ’703 patent col. 23 ll. 45
to col. 24 l. 6. Second, and more importantly, the ’703
patent refers to a “substantially pure regioisomer” of a
specific formula. ’703 patent col. 24 l. 8. Notwithstanding,
the term “substantially pure” is not defined anywhere in
the specification, as noted by the district court.
11                           AVENTIS PHARMA   v. MYLAN PHARMA

c.   The “Providing” and “Converting” Steps

    The “providing” and “converting” steps of the method
in claim 1 of the ’703 patent are illuminated by dependent
claims 2, 3, 4, and 5, as well as the patent specification.
The dependent claims and the specification examples
teach multiple methods for “providing” the para-CPK
intermediate, both as a substantially pure para-CPK
product or as a mixture of para-CPK and meta-CPK
products. See, e.g., ’703 patent col. 12 l. 65 to col. 19 l. 35
(specification); col. 24 l. 35 to col. 25 l. 62 (claims 2-5). For
example, dependent claims 2 and 3 describe an acylation
and purification process that results in the recovery of the
para-CPK intermediate from a “second mixture of regioi-
somers”. ’703 patent col. 24 l. 35 to col. 25 l. 53 (claims 2-
3). Example 2 of the specification, on the other hand,
describes another “providing” teaching, producing a
“crude product” that is a mixture of para-CPK and meta-
CPK that could be further purified to predominantly
para-CPK. ’703 patent col. 19 l. 65 to col. 20 l. 19. Exam-
ple 2, however, never requires further regioisomeric
purification to a specific level. See id. In fact, nowhere
in the specification is any numeric value attached to the
purity of the CPK intermediate.

     “Converting” is the coupling reaction of the para-CPK
to azacyclonol to create the end-product piperidine deriva-
tive. Again, the specification describes multiple processes
for performing the claimed step of “converting” the CPK
intermediate to a piperidine derivative compound. See
’703 patent col. 16 l. 31 to 18 l. 67. As with “providing”
the CPK intermediate, the “converting” step does not
indicate that the CPK intermediate must be in a substan-
tially pure form, or even provide any required level of
purity.
AVENTIS PHARMA   v. MYLAN PHARMA                         12

             2. Claim 6 of the Patents-in-Suit

    While claim 1 describes a process for producing piper-
idine derivatives through use of a CPK intermediate
generally, claims 6 and 7 further specify the piperidine
derivative end product synthesized by the patented pro-
cess. Dependent claim 6 describes:

    6. A process according to claim 1 further compris-
    ing:

    reducing the piperidine derivative under condi-
    tions effective to form a hydroxylated piperidine
    derivative of the formula:

’703 patent col. 25 l. 63 to col. 26 l. 15 (Claim 6).

             3. Claim 7 of the Patents-in-Suit

    Dependent claim 7 further specifies the type of hy-
droxylated piperidine derivative end product of claim 6—
fexofenadine:

    7. A process according to claim 6, wherein the hy-
    droxylated piperedine derivative has the formula:
13                        AVENTIS PHARMA   v. MYLAN PHARMA

’703 patent col. 26 ll. 16–33 (Claim 7). Thus, Claim 7 of
the ’703 patent produces an important active pharmaceu-
tical ingredient and was the claim asserted against the
generic manufacturers’ accused antihistamines.

                 4. Prior Art Processes

    The Background section of the ’703 patent discusses
in detail the prior art processes for making piperidine
derivatives. The patented process claimed in the ’703
patent represented a significant improvement over these
prior art processes, in particular the method taught in
U.S. Patent No. 4,254,129 (“the ’129 patent”), which
issued on March 3, 1981.

    The process disclosed in the ’129 patent used a
“Friedel-Crafts” reaction to arrive at a piperidine deriva-
tive. See ’703 patent col. 2 ll. 27–41. The Friedel-Crafts
reaction produced a statistical admixture, termed the
“second mixture of aromatic regioisomers” by the ’703
patent, containing 67% meta-isomer of the piperidine
derivative end product and 33% para-isomer of the piper-
idine derivative end product: 7

     7 The illustrated bond extending into the lower ar-
omatic ring indicates a mixture of para- and meta-
isomers. See ’703 patent col. 3 ll. 15–30.
AVENTIS PHARMA    v. MYLAN PHARMA                            14

See, e.g., ’703 patent col. 2 l. 42 to col. 4 l. 25. The “second
mixture of aromatic regioisomers” could then be converted
to a “third mixture of regioisomers” of the following
formula:

’703 patent, col. 3 l. 65 to col. 4 l. 25.

    Dr. D’Ambra discovered in the course of attempting to
replicate the teaching of the ’129 patent that it was prac-
tically impossible to completely separate the para-isomer
of the piperidine derivative product to pharmaceutical
purity when using the ’129 patent’s process. In order to
improve the regioisomeric purity more easily at an earlier
stage in the reaction, D’Ambra developed the patented
15                        AVENTIS PHARMA   v. MYLAN PHARMA

process discussed above; in particular, he discovered the
novel use of the para-CPK intermediate. By using his
unique starting material, a purer regioisomeric form of
the CPK intermediate, the regioisomeric purity of the end
product could be much higher than the 33% para-CPK
produced by the ’129 patent’s process. Dr. D’Ambra
discovered a different process of synthesizing a piperidine
derivative product to higher regioisomeric purity; then by
using recrystallization and other purification techniques,
he could attain pharmaceutical-grade fexofenadine at a
much lower expense.

               B. Procedural Background

    The larger procedural history is complex, involving
dozens of parties in twenty cases. It suffices to limit the
discussion to Defendant-Appellees, Amino Chemicals
Ltd., Dipharma Francis, Sr.L., and Dipharma Spa (collec-
tively “Appellees”). Appellees are generic drug manufac-
turers. Amino Chemicals had filed a Drug Master File
that was referenced in Abbreviated New Drug Applica-
tions (“ANDAs”) of two former parties, Mylan Pharmaceu-
tical Inc. and Teva Pharmaceuticals USA, Inc., which had
sought Food and Drug Administration (“FDA”) approval
to market antihistamines containing fexofenadine. Simi-
larly, Dipharma Francis and Dipharma Spa are bulk-
manufacture suppliers of Mylan and Teva. Upon submis-
sion of the ANDAs to the FDA, Appellants timely brought
several suits against the generic drug manufacturers in
the New Jersey district court, alleging, inter alia, in-
fringement of the ’703 patent.

    The district court performed a tentative claim con-
struction in connection with a September 20, 2005 motion
for a preliminary injunction filed after Teva began mar-
keting a generic fexofenadine drug. Judge Greenaway’s
January 30, 2006 opinion denied the preliminary injunc-
AVENTIS PHARMA   v. MYLAN PHARMA                         16

tion request, and set forth an initial claim construction of
the ’703 patent’s disputed claim term “substantially
pure.” See Aventis Pharms., Inc. v. Barr Labs., Inc., 411
F. Supp. 2d 490, 509 (D.N.J. 2006). The district court
found that the ’703 patent’s specification used the phrase
“substantially pure” to describe both the piperidine deriv-
ative end products and the CPK intermediate. Id. at 498-
99. The district court also relied on statements from the
prosecution history regarding the purity of the piperidine
derivative end products to reach a tentative claim con-
struction that the phrase “substantially pure” in the
asserted claims of the ’703 patent means “of greater than
95% purity.” Id. at 502–03. The court extended this to
describe not only the purity level necessary of end prod-
ucts, but also the CPK intermediate compound. Id. In
declining to institute a preliminary injunction based on
the ’703 patent, the district court did not reach the issue
of whether “substantially pure” describes overall chemical
purity as to everything in the compound or whether the
term is limited to regioisomeric purity, i.e., the purity
only of the para-isomer relative to unwanted meta-isomer.
Id. at 508.

    The parties thereafter filed opening and responsive
claim construction briefs, and on November 10, 2010, a
Markman hearing was held before Chief Judge Brown.
The Markman Opinion issued on January 13, 2010,
construing two terms from the ’703 patent relevant here.
Joint App’x 41; see also Aventis Pharms., Inc. v. Impax
Labs., Inc., Nos. 02-1322, 03-1179, 03-1180, 03-5108, 03-
5829, 04-1075, 04-1076, 04-1077, 04-1078, 04-2305, 04-
3194, 05-4255, 06-5463, 07-5054, 07-5180, 09-0325, 09-
4638, 09-5179, 10-1471, 2011 WL 2175928, at *1 (D.N.J.
Jan. 31, 2011) (publically available Markman opinion).
17                         AVENTIS PHARMA     v. MYLAN PHARMA

     From claim 1 of the ’703 patent, the district court con-
strued the terms “substantially pure regioisomer of the
following formula

                                          ”
and “substantially pure.” The district court held that
neither the claims nor the specification give sufficient
specific guidance as to the meaning of either claim term.
The trial court found, however, that the specification
“indiscriminately” equates the purity of the intermediates
and final products to such an extent that there is no
justification to differentiate between “substantially pure”
para-CPK intermediates and “substantially pure” piperi-
dine derivative end products. According to the court:
“[B]ecause the specification uses the same term consist-
ently for both intermediates and derivatives, the Court
finds that what ‘substantially pure’ means when it modi-
fies the piperidine derivative applies equally to its context
in the claims’ ‘substantially pure regioisomer of the
formula.’” Joint App’x 49; see also Aventis, 2011 WL
2175928, at *5.

    Regarding what “substantially pure” actually means
when applied to both the CPK intermediate and piperi-
dine derivative end product, the district court was forced
to rely on the prosecution history of the ’703 patent, as
well as the prosecution history of the related U.S. Patent
No. 5,578,610 (filed June 24, 1993) (“the ’610 patent”),
which is another divisional descended from the parent
08/083,102 application. The district court determined
through the prosecution history that “the inventor under-
stood the term ‘substantially pure’ to mean 98% purity
AVENTIS PHARMA   v. MYLAN PHARMA                         18

and that the inventor clearly and unambiguously disa-
vowed any other claim scope.” Joint App’x 52; see also
Aventis, 2011 WL 2175928, at *7.

    To arrive at this particularly high level of purity, the
district court cited to a statement made by Dr. D’Ambra
during the ’610 patent interference in 1997. There, Dr.
D’Ambra allegedly stated several times that “substantial-
ly pure” meant pharmaceutical-grade, or 98%, purity of
end products for consumption. From this—despite ac-
knowledging that the statements were likely only describ-
ing end-products—the district court concluded that “it is
clear that by ‘substantially pure’ the patentee meant
pharmaceutical-grade purity, which requires an impurity
level no greater than 2%. These statements both explain
the meaning the patentee assigned to ‘substantially pure’
and represent a clear disclaimer of patent scope for his
patent.” Joint App’x 54; see also Aventis, 2011 WL
2175928, at *8. Thus, by virtue of the specification’s
nondiscrimination between intermediates and end prod-
ucts, a 98% purity requirement was extended to the para-
CPK intermediate as well.

    Finally, with regard to “substantially pure,” the court
held that 98% purity refers to chemical impurities of any
kind present in the product, not just regioisomeric impu-
rity. Joint App’x 55 (“The plain language of the term
‘substantially pure’ is relative to all impurities—a solu-
tion of 25% para-CPK, 0.2% meta-CPK, and 74.8% dirt
would not be substantially pure.”); see also Aventis, 2011
WL 2175928, at *8.

     In sum, the district court construed the relevant
terms at issue from the ’703 patent so that (1) “substan-
tially pure” means “at least 98% purity with respect to all
impurities” and (2) “providing regioisomer of the following
formula
19                        AVENTIS PHARMA   v. MYLAN PHARMA

                                           ”
means “the regioisomer having the structure shown in the
formula is present in at least 98% purity with respect to
all impurities.” Joint App’x 65; see also Aventis, 2011 WL
2175928, at *13. In light of this claim construction,
Appellants stipulated that they could no longer prove
infringement, and the district court entered final judg-
ment in favor of Appellees in both cases. Appellants
timely appealed the disputed claim construction of the
’703 patent to this court. We have jurisdiction pursuant
to 28 U.S.C. § 1295(a)(1).

                     II. DISCUSSION

    Claim construction is an issue of law since Markman
v. Westview Instruments, Inc., 52 F.3d 967, 981 (Fed. Cir.
1995) (en banc), aff'd, 517 U.S. 370 (1996). This court
reviews district court claim constructions de novo. Cybor
Corp. v. FAS Techs., Inc., 138 F.3d 1448, 1456 (Fed. Cir.
1998) (en banc).

    “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.” Phillips v. AWH Corp., 415
F.3d 1303, 1312 (Fed. Cir. 2005) (en banc) (internal
quotation marks omitted). There is a heavy presumption
that claim terms are to be given their ordinary and cus-
tomary meaning. Id. at 1312–13; Vitronics Corp. v.
Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996).
Courts are required therefore to “look to the words of the
claims themselves . . . to define the scope of the patented
AVENTIS PHARMA   v. MYLAN PHARMA                         20

invention.” Id.; see also Toro Co. v. White Consol. Indus.,
Inc., 199 F.3d 1295, 1299 (Fed. Cir. 1999).

     Claims, however, must be construed in light of the
appropriate context in which the claim term is used. See
Toro, 199 F.3d at 1299. The written description and other
parts of the specification, for example, may shed contex-
tual light on the plain and ordinary meaning; however,
they cannot be used to narrow a claim term to deviate
from the plain and ordinary meaning unless the inventor
acted as his own lexicographer or intentionally disclaimed
or disavowed claim scope. Id. at 1316; cf. Markman, 52
F.3d at 980 (“[T]he written description part of the specifi-
cation itself does not delimit the right to exclude. That is
the function and purpose of claims.”). The prosecution
history too, as part of the intrinsic record, has an im-
portant role in claim construction by supplying context to
the claim language. While the prosecution history “lacks
the clarity of the specification and thus is less useful for
claim construction purposes”, Phillips, 415 F.3d at 1317,
it still provides evidence of how the inventor intended the
term to be construed. See Lemelson v. Gen. Mills, Inc.,
968 F.2d 1202, 1206 (Fed. Cir. 1992).

                 A. “Substantially Pure”

    Claims 1, 6, and 7 of the ’703 patent explicitly include
the term “substantially pure regioisomer.” The district
court construed this language to require “at least 98%
purity with respect to all impurities.” This construction,
however, conflates the purity required for the piperidine
end product with that of the CPK intermediate.
21                        AVENTIS PHARMA   v. MYLAN PHARMA

  1. CPK Intermediate Versus Piperidine End Product

    We agree with both parties that the claims them-
selves are insufficient to define the term “substantially
pure.” Therefore, we must turn to other sources of intrin-
sic evidence to determine “what the inventors actually
invented and intended to envelop with the claim.” Ren-
ishaw PLC v. Marposs Societa’ per Azioni, 158 F.3d 1243,
1250 (Fed. Cir. 1998). The specification provides the “best
source” for construing a claim term and determining the
inventor’s intent regarding use. Multiform Dessicants,
Inc. v. Medzam, Ltd., 133 F.3d 1473, 1478 (Fed. Cir.
1998); see also Vitronics, 90 F.3d at 1582.

    In this case, the specification does not provide an ex-
plicit definition of the term “substantially pure” or “sub-
stantially pure regioisomer.”         The district court
determined that because the term “substantially pure” is
used indiscriminately with regards to the CPK intermedi-
ate and the piperidine derivative end product throughout
the specification, “substantially pure” should have only
one construction throughout the patent. The “one con-
struction throughout the patent” rule adopted by the
district court is incorrect.

    We have previously held that the same claim term
can have different constructions depending upon the
context of how the term is used within the claims and
specification. See Microprocessor Enhancement Corp. v.
Tex. Instruments, Inc., 520 F.3d 1367, 1375 (Fed. Cir.
2008) (holding that, while there is a presumption that a
claim term will be construed consistently when used
throughout the claims, there is no requirement that a
claim term be construed uniformly, particularly if it
would lead to a “nonsensical reading”). In Epcon Gas
Systems, Inc. v. Bauer Compressors, Inc., 279 F.3d 1022
AVENTIS PHARMA   v. MYLAN PHARMA                        22

(Fed. Cir. 2002), for example, we construed the term
“substantially” to have different interpretations based on
a “subtle but significant difference” in context and usage.
Id. at 1030–31.

    While “substantially pure” refers to both the CPK in-
termediate and the piperidine derivative end product in
the specification, the term “substantially pure” is used
only in reference to the CPK intermediate in relevant
claims 1, 6, and 7. And unlike other patents in the fami-
ly, there is no explicit “substantially pure” limitation
placed on the piperidine derivative end product in the
relevant claims of the ’703 patent. The lack of any “sub-
stantially pure” limitation on the piperidine derivative
end products in claims 1, 6, and 7 obviates any explicit
requirement to apply a construction of “substantially
pure” that is consistent for both the CPK intermediate
and the piperidine derivative end product.

    Further, a person of ordinary skill in the art would
recognize that an intermediate of the claimed chemical
reaction would not be required to have the same purity as
the end product. As mentioned in the specification, both
in reference to the prior art ’129 patent and also through-
out the examples, various crystallization and purification
processes are available to purify the piperidine derivative
end product to reach pharmaceutical-grade purity after
synthesis. The ’703 patent represents an improvement
over the prior art processes. The improvement was not
that the patented technique could guarantee a piperidine
derivative of pharmaceutical purity absent further purifi-
cation; the improvement was that the patented technique
could provide a piperidine derivative end product of
higher regioisomeric purity requiring less extensive
purification than the end product derived by the process
23                         AVENTIS PHARMA   v. MYLAN PHARMA

of the ’129 patent. 8 Reading “substantially pure” to
require a consistent construction for the CPK intermedi-
ate and piperidine derivative end product ignores the
distinct contexts in which these terms are used.

    Appellees argue that reading a common term to have
different meanings in different contexts does not apply
here to the interpretation of “substantially pure.” They
distinguish Epcon and Microprocessor because the pa-
tents in those cases contained intrinsic records which
clearly and expressly supported multiple interpretations
for a single claim term. Appellees maintain that no such
clear and express support is found in the ’703 patent
specification at issue. But this ignores that we must
always construe the specification in light of the
knowledge of one of ordinary skill in the art. Phillips, 415
F.3d 1313. Through basic knowledge of chemical reac-
tions and purification schemes, a skilled artisan would
recognize that the purity of an intermediate compound in
a reaction is often not equivalent to the purity of the end
product, especially when further, common physical purifi-
cation steps may be necessary. Interpreting this specifi-
cation in light of the knowledge of a person of ordinary
skill in the art, we hold that a proper construction re-
quires different interpretations of “substantially pure”
when applied to the CPK intermediate and piperidine
derivative end product.

     The “one-size-fits-all” construction adopted by the dis-
trict court incorrectly construes “substantially pure”
separate from the very next word--“regioisomer.” The

     8   The process described in the ’129 patent did not
appear to be able to reach a purity of greater than 95%
without resorting to exceptionally difficult and cost-
ineffective techniques. See supra Part I.A.4.
AVENTIS PHARMA   v. MYLAN PHARMA                              24

district court’s artificial truncation of the claim term for
the expediency of a single interpretation across different
contexts was error. Outside of the description of the prior
art process from the ’129 patent, the specification almost
exclusively uses the term “regioisomer” to refer to the
CPK intermediate. Further, the full term, “substantially
pure regioisomer,” is used only in reference to the CPK
intermediate. See ’703 patent col. 5 ll. 11–12, 23, 40–41;
col. 12 ll. 32–33, 43, 62–66; col. 13 ll. 55–56; col. 13 l. 67 to
col. 14 ll. 37–38, 51, 53; col. 15 ll. 13–14, 51–52, 54; col. 16
ll. 21–22, 25–26, 31–32, 34–35, 49; col. 18 ll. 4–5, 7–8.
Such uniform use of “substantially pure regioisomer,”
taken as a whole, exposes the error of the district court:
by decoupling the modifier “substantially pure” from
“regioisomer” for purposes of claim construction, the
district court imposed a single interpretation even though
that context requires separate definitions of “substantial-
ly pure” when applied to the CPK intermediate as op-
posed to the piperidine derivative end product. We thus
conclude that the district court erred in requiring that
“substantially pure” have the same interpretation when
applied to the CPK intermediate and the piperidine
derivative end product.

  2. Construction of “Substantially Pure Regioisomer”

    Although it was error for the district court to limit the
construed term to encompass both the CPK intermediate
and the piperidine derivative end product, the proper
term to construe, “substantially pure regioisomer,” still
requires claim construction. The presumption is that
claim terms should be given their “ordinary and custom-
ary meaning,” Vitronics, 90 F.3d at 1582, and not a re-
strictive construction unless there is clear evidence to
support it in the intrinsic evidence, or a broader meaning
is specifically disclaimed during prosecution. See Saun-
ders Grp., Inc. v. Comfortrac, Inc., 492 F.3d 1326, 1331
25                        AVENTIS PHARMA   v. MYLAN PHARMA

(Fed. Cir. 2007). A court can look to the prosecution
history of related patents for guidance in claim construc-
tion. See Ormco Corp. v. Align Tech., Inc., 498 F.3d 1307,
1314 (Fed. Cir. 2007).

    The district court interpreted “substantially pure” in
isolation to mean “at least 98% purity with respect to all
impurities” based in large part on the prosecution history
of the related ’610 patent. The district court looked to
statements made during the ’610 patent’s interference
proceedings before the U.S. Patent and Trademark Office
(PTO), where the patentee stated that a person of ordi-
nary skill in the art would understand “substantially
pure” in claims 1-17 to refer to pharmaceutical-grade
purity. Claims 1-17 include claims, such as claim 12,
where “substantially pure” modifies only the CPK inter-
mediate. On that basis, the district court concluded here
that “substantially pure” as applied to the CPK interme-
diate required “at least 98% purity with respect to all
impurities.”

    In analyzing the claims of the ’703 patent, we find
statements made in the ’610 patent’s interference pro-
ceedings of little help. The patentee and the PTO both
explicitly noted that the focus of the ’610 patent’s inter-
ference was limited to interpreting the claims in reference
to the piperidine end product. Even the statements made
by Dr. D’Ambra 9 were made specifically in regards to the
“subject compound” of the interference, which was only
the end product. At most, the construction of “substan-

     9  The statements made by Dr. D’Ambra during the
‘610 patent’s interference proceedings were the focal point
of the district court’s and defendant’s application of “at
least 98% purity with respect to all impurities” to the
CPK intermediate.
AVENTIS PHARMA   v. MYLAN PHARMA                        26

tially pure” derived from the ’610 patent’s interference
applies to the piperidine derivative end product, not the
CPK intermediate at issue in this case. Since we have
found that “substantially pure” has different construc-
tions when applied to the CPK intermediate and the
piperidine end product in the ’703 patent, there is no
justification for applying the definition of “substantially
pure” from the ’610 patent’s interference to “substantially
pure regioisomer” in the ’703 patent.

    In determining the scope of the claim term “pure,” the
district court further assumed that “substantially pure”
must apply to all impurities present in solution, not just
regioisomeric purity. The district court reasoned that the
plain language of “substantially pure” must involve all
impurities, because “a solution of 25% para-CPK, 0.2%
meta-CPK, and 74.8% dirt would not be substantially
pure.” Joint App’x 55; see also Aventis, 2011 WL 2175928,
at *8. This flawed analysis again does not consider the
appropriate frame of reference for claim construction. A
person of ordinary skill in the art would recognize that
the ’703 patent improved the regioisomeric purity of the
end product that results from the claimed reaction as
compared to the Friedel-Crafts acylation disclosed in the
’129 patent. For example, in the district court’s hypothet-
ical mixture “of 25% para-CPK, 0.2% meta-CPK, and
74.8% dirt,” the patented reaction could very well produce
25% para-piperidine derivative end product, 0.2% meta-
piperidine derivative end product, and 74.8% “dirt.” The
“dirt” could then be removed through simple purification
processes, such as crystallization, leaving 99.2% para-
piperidine derivative end product and 0.8% meta-
piperidine derivative end product. Such an end product
mixture would arrive at the standard for pharmaceutical-
grade purity even though the “dirt” represented a sub-
stantial impurity in the early stages of the reaction.
Again, the weakness in the ’129 patent was its inability to
27                        AVENTIS PHARMA   v. MYLAN PHARMA

produce an end product with a 125:1 ratio 10 of para- to
meta-piperidine derivative, or even anything approaching
such a ratio. It was this inherent deficiency of the ’129
patent’s process in regioisomeric purity that the ’703
patent improved upon. Further, the processes disclosed
in the ’129 and’703 patents consider the need for further
purification steps after the claimed reactions. While
these purification steps will help improve the ratio of
para- to meta-piperidine product, they will also remove
other reaction impurities. Therefore, the general purity of
other reaction components in the CPK-mixture is largely
irrelevant at the intermediate stage. The district court
actually recognized this point to a lesser extent, noting
that “with respect to all impurities” does not include
“intended elements of solutions, such as solvents, cata-
lysts and other compounds.” We hold that the modifier
“substantially pure,” when construed in light of a person
of ordinary skill in the art and in view of the claimed
improvements over the prior art, only applies regioiso-
meric impurities, not all impurities.

               3. Appellants’ Construction

    With no explicit construction of the term “substantial-
ly pure” in the claims, specification, or prosecution histo-
ry, we apply the “ordinary and customary” definition to
the claim term. In other contexts, this court has inter-
preted “substantially” as a non-specific term of approxi-
mation that avoids a numerical boundary. See, e.g.,
Playtex Prods., Inc. v. Procter & Gamble Co., 400 F.3d
901, 907 (Fed. Cir. 2005); Liquid Dynamics Corp. v.
Vaughan Co., 355 F.3d 1361, 1368 (Fed. Cir. 2004) (“The
term ‘substantial’ is a meaningful modifier implying

      25% para-piperidine derivative end product to
     10

0.2% meta-piperidine derivative end product.
AVENTIS PHARMA   v. MYLAN PHARMA                          28

‘approximate,’ rather than ‘perfect.’”); Cordis Corp. v.
Medtronic Ave, Inc., 339 F.3d 1352, 1360 (Fed. Cir. 2003);
Ecolab, Inc. v. Envirochem, Inc., 264 F.3d 1358, 1366–67
(Fed. Cir. 2001).

    In the context of “substantially pure” as applied to a
CPK intermediate, “substantially” would also not be
amenable to a numerical boundary. The ’703 patent
implies that the regioisomeric purity should be greater
than 67%, ’703 patent col. 4 ll. 15–25, but the patent
specification tellingly does not list any necessary mini-
mum purity for the CPK intermediate in order to produce
a desired piperidine derivative end product with pharma-
ceutical-grade purity. As described in the patent, a
piperidine derivative end product with a regioisomeric
purity below 98% can be purified through crystallization
or other physical techniques to reach pharmaceutical-
grade purity, showing that the CPK intermediate does not
itself need to be at a regioisomeric purity of 98% or high-
er. ’703 patent col. 13 l. 55 to col. 14 l. 14.

    Appellants propose that “substantially pure regioiso-
mer of the following formula” should be construed as
“largely but not wholly the para regioisomer of the inter-
mediate of the structure shown, as compared to the meta
isomer.” Appellants’ Br. 10. This construction of “sub-
stantially” was previously applied with approval in
Ecolab, 264 F.3d at 1366 (noting that Webster’s Ninth
New Collegiate Dictionary, 1176 (9th ed. 1983), defines
“substantially” to mean “largely but not wholly that which
is specified”). “Largely but not wholly” is consistent with
a flexible approach to regioisomeric purity for an inter-
mediate, is faithful to the specification’s silence regarding
numerical precision and, most importantly, is not arbi-
trarily tied to the FDA standard for pharmaceutical-grade
end products. No one ingests the intermediate compound,
so there is no reason to impose end-product purity on it.
29                        AVENTIS PHARMA   v. MYLAN PHARMA

Therefore, we adopt the Appellants’ proposed construction
of “substantially pure regioisomer of the following formu-
la” as used in the ’703 patent and construe the term to
mean “largely but not wholly the para regioisomer of the
intermediate of the structure shown, as compared to the
meta isomer.”

                     III. CONCLUSION

    Because the district court erred in construing “sub-
stantially pure” as used in the ’703 patent, we reverse and
remand.

             REVERSED AND REMANDED

                          COSTS

     No costs.
 United States Court of Appeals
     for the Federal Circuit
     AVENTIS PHARMACEUTICALS INC.,
             Plaintiff-Appellant,

                       AND

          AMR TECHNOLOGY, INC.,
  (now known as Albany Molecular Research, Inc.),
               Plaintiff-Appellant,

                        v.

AMINO CHEMICALS LTD., DIPHARMA FRANCIS,
        SR.L., AND DIPHARMA SPA,
            Defendants-Appellees,

                       AND

      MYLAN PHARMACEUTICALS INC.,
               Defendant.

             -------------------

     AVENTIS PHARMACEUTICALS INC.,
             Plaintiff-Appellant,

                       AND

          AMR TECHNOLOGY, INC.,
  (now known as Albany Molecular Research, Inc.),
               Plaintiff-Appellant,

                        v.
1                         AVENTIS PHARMA   v. MYLAN PHARMA

       TEVA PHARMACEUTICALS USA, INC.,
                 Defendants,

                           AND

AMINO CHEMICALS LTD., DIPHARMA FRANCIS,
        SR.L., AND DIPHARMA SPA,
            Defendants-Appellees.

                 ______________________

                    2011-1335,-1336
                 ______________________

    Appeals from the United States District Court for the
District of New Jersey in Nos. 04-CV-1075, 04-CV-1077,
and 04-CV-1078, Chief Judge Garrett E. Brown Jr.
               __________________________

BRYSON, Circuit Judge, dissenting.

     The majority concludes that the district court erred in
its construction of the term “substantially pure” in claim 1
of U.S. Patent No. 5,750,703 (“the ’703 patent”) and
therefore reverses the district court’s judgment. I would
uphold the district court’s construction of that term, and I
therefore respectfully dissent.

                             I

     The district court construed the term “substantially
pure” to mean “at least 98% purity with respect to all
impurities.” In arriving at that construction, the court
first determined that “substantially pure” has the same
meaning whether it refers to the piperidine derivative end
product or the para-CPK intermediate. The court noted
AVENTIS PHARMA   v. MYLAN PHARMA                          2

that the “inventor uses the phrases ‘substantially pure’
and ‘substantially pure regioisomers’ indiscriminately to
refer to both final products and intermediates. There is
no evidence that the inventor intended the term to mean
different things.” Based on the prosecution histories of
the ’703 patent and related U.S. Patent No. 5,578,610
(“the ’610 patent”), 1 the court then held that the term
“substantially pure” refers to pharmaceutical grade
purity, i.e., 98% pure. Finally, the court determined that
the required purity level was to be measured with respect
to all impurities, not just the unwanted meta-CPK, except
that the 98% purity level did not include “intended ele-
ments of solutions such as solvents, catalysts, or other
compounds that are not considered impurities.”

     Aventis’s primary argument on appeal is that the
term “substantially pure” should be given a different
meaning when it refers to the para-CPK intermediate,
which the claim describes as a “substantially pure regioi-
somer” of CPK, than when it refers to the piperidine
derivative end product. Aventis essentially concedes that
if the term at issue were “substantially pure end product,”
98% purity with respect to all impurities would be an
accurate construction. But since the term “substantially
pure” is used in claim 1 to refer to the “substantially pure
regioisomer”—i.e., the para-CPK intermediate—Aventis
argues that a different construction is required. Aventis
contends that the evidence relied upon by the district
court pertained only to the purity of the end product, and
that the term “substantially pure” has a different mean-
ing when used to refer to intermediates than when used

   1    The application that issued as the ’610 patent was
filed as a division of the application that issued as the
’703 patent, and the two specifications are essentially the
same.
3                         AVENTIS PHARMA   v. MYLAN PHARMA

to refer to end products. As used in reference to the
regioisomer, Aventis argues that the term “substantially
pure” means “largely but not wholly [para-CPK], as
compared to [meta-CPK].”

     The majority embraces Aventis’s proposed construc-
tion, holding that the patent gives the term “substantially
pure” different meanings when referring to the terms
“substantially pure regioisomer” and “substantially pure
piperidine derivative.” As the district court ruled, howev-
er, the intrinsic evidence does not distinguish between the
way “substantially pure” is used with respect to those two
terms, and for that reason I would uphold the district
court’s claim construction.

    In seeking to distinguish between the meaning of the
term “substantially pure” when it is applied to the inter-
mediate regioisomer as opposed to when it is applied to
the piperidine derivative end product, Aventis relies on
the argument that one of ordinary skill in the art would
know that the purity of intermediates may be different
from the purity of end products, and it offers expert
testimony in support of that proposition. But even if a
person of ordinary skill in the art would not necessarily
regard purity as meaning the same thing for an interme-
diate as for an end product, the analysis does not end
there.

    In at least two places, the intrinsic record uses the
term “substantially pure” in the same way with regard to
the regioisomer and the end product. First, the specifica-
tion states:

    Although the second mixture of regioisomers [an
    intermediate] and the third mixture of regioiso-
    mers [the final piperidine derivative product] can
    be analyzed by HPLC experiments, a practical
AVENTIS PHARMA   v. MYLAN PHARMA                          4

   separation to obtain gram quantities of substan-
   tially pure regioisomers has not been achieved.

   Each mixture (including the first [also an inter-
   mediate]), would be expected to contain 33% of the
   para isomer and 67% of the meta isomer. Since
   these components are inseparable, it has not been
   possible to obtain either of the regioisomers in
   each [first, second, and third] mixture in substan-
   tially pure form.

’703 patent at col. 4 ll. 16-24 (emphasis added). Second,
in an interference involving the related ’610 patent, the
patentee wrote:

   When read in light of the specification, one skilled
   in the art would have understood that the phrase
   “substantially pure”, as used in claims 1-17 of the
   D'Ambra Patent [the ’610 patent], to mean that
   the subject compound has pharmaceutical grade
   purity and is in a form purer than that attained
   by the prior art (e.g., U.S. Patent Nos. 4,254,129,
   4,254,130, 4,285,957, and 4,285,958 to Carr (col-
   lectively, “the Carr Patents”). As demonstrated,
   infra, those skilled in the art recognized that
   pharmaceutical grade purity requires an impurity
   level no greater than 2%, and the Carr Patents
   were unable to achieve such purity.

    Importantly, that response refers to claims 1-17 of the
’610 patent; one of those claims, claim 12, recites, “a
piperidine derivative compound produced by a process
comprising: providing a substantially pure regioisomer . . .
.” (emphasis added).

    Aventis concedes that in the first passage the patent-
ee failed to distinguish between the use of “substantially
5                          AVENTIS PHARMA   v. MYLAN PHARMA

pure” as applied to an intermediate and to an end prod-
uct, but it claims that the passage is irrelevant because it
concerns the prior art Carr process. In fact, however,
both the discussion of the prior art and the discussion of
the claimed invention use the term “substantially pure”
when referring to regioisomers; one of the “mixture[s]”
referenced in the second paragraph is CPK, while another
is the piperidine end product. Thus, the patentee fails to
distinguish between “substantially pure regioisomer” and
“substantially pure [end product],” and in fact affirma-
tively suggests that the meaning of “substantially pure”
does not turn on whether it modifies “regioisomer” or
“piperidine derivative [end product].”

     Regarding the second reference, Aventis argues that it
is clear in context that the passage concerns the purity of
the end product. Aventis also argues that the “subject
compound” described in that passage is the end product,
making clear that the discussion of “substantially pure” in
that passage applies only to the end product. The prob-
lem with Aventis’s position is that the quoted language
expressly refers to “‘substantially pure’ . . . as used in
claims 1-17,” and claim 12 of the ’610 patent refers to a
“substantially pure regioisomer.” Thus, “‘substantially
pure’ . . . as used in claims 1-17” unequivocally includes
“substantially pure regioisomer.” That reference thus
rebuts Aventis’s claim that the patentee was careful to
distinguish between “substantially pure regioisomer” and
“substantially pure piperidine derivative [end product].”
The patentee could have written “‘substantially pure
piperidine derivative’ . . . as used in claims 1-17,” but it
chose not to, referring only to “‘substantially pure’ . . . as
used in claims 1-17.” Those two examples show that the
patentee did not intend for the term “substantially pure”
to have a different meaning depending on whether it was
describing an intermediate or an end product.
AVENTIS PHARMA   v. MYLAN PHARMA                          6

     Beyond those two passages, the intrinsic record pro-
vides little else of help in construing the term “substan-
tially pure.”     However, general principles of claim
construction are instructive here. “[W]e presume, unless
otherwise compelled, that the same claim term in the
same patent or related patents carries the same construed
meaning.” Omega Eng’g, Inc. v. Raytek Corp., 334 F.3d
1314, 1334 (Fed. Cir. 2003); see also Paragon Solutions,
LLC v. Timex Corp., 566 F.3d 1075, 1087 (Fed. Cir. 2009)
(“We apply a presumption that the same terms appearing
in different portions of the claims should be given the
same meaning unless it is clear from the specification and
prosecution history that the terms have different mean-
ings at different portions of the claims.”). Starting with
the presumption that “substantially pure” means the
same thing when describing “regioisomer” as it does when
describing “piperidine derivative,” it is clear that Aventis
has not put forth “compell[ing]” evidence to the contrary. 2
Indeed, as noted above, the intrinsic record supports the
district court’s finding that “substantially pure” has the
same meaning throughout the patent, and Aventis has
pointed to nothing compelling in the record to suggest

   2    The majority cites two of our cases for the proposi-
tion that the same term in a patent can have different
meanings—Microprocessor Enhancement Corp. v. Tex.
Instruments Inc., 520 F.3d 1367, 1376 (Fed. Cir. 2008),
and Epcon Gas Sys., Inc. v. Bauer Compressors, Inc., 279
F.3d 1022, 1030-31 (Fed. Cir. 2002). In both of those
cases, however, there was a clear basis in the intrinsic
record for applying different meanings to the same term.
By contrast, there is no compelling evidence that “sub-
stantially pure” was intended to mean different things
with respect to “regioisomer” and “piperidine derivative.”
7                          AVENTIS PHARMA   v. MYLAN PHARMA

otherwise. 3 Aventis’s reliance on expert testimony that
one of ordinary skill in the art would know that “substan-
tially pure” can mean different things when describing
intermediates than when describing end products is not
enough to overcome the persuasive intrinsic record in this
case. See Kara Tech. Inc. v. Stamps.com Inc., 582 F.3d
1341, 1348 (Fed. Cir. 2009) (“While helpful, extrinsic
sources like expert testimony cannot overcome more
persuasive intrinsic evidence.”).

    Aventis’s expert testimony does not indicate that
“substantially pure regioisomer” is a term of art that
connotes a specific level of purity relative to that of the
end product. Thus, although “substantially pure” certain-
ly could have different meanings in different contexts,
there is no evidence indicating that it must mean some-
thing different when used to describe a regioisomer as
opposed to an end product. The majority bases its con-
struction of the term “substantially pure regioisomer” on
the general definition of the term “substantially,” which is
taken from an unrelated case that in turn cites a general
dictionary definition. That appeal to extrinsic evidence
from outside the art underscores the fact that Aventis has
offered nothing in the intrinsic record, or even in the state
of the art, to define the term that is the focus of the

    3    The majority also suggests the presumption of
consistent claim construction does not apply in this case
because “there is no explicit ‘substantially pure’ limitation
placed on the piperidine derivative end product in the
relevant claims of the ’703 patent.” However, the term
“substantially pure” limits the claimed end product in the
related ’610 patent, so the presumption applies here. See
Omega Eng’g, Inc., 334 F.3d at 1334 (applying presump-
tion of consistency to “the same claim term in . . . related
patents”).
AVENTIS PHARMA   v. MYLAN PHARMA                          8

parties’ dispute. Instead of resorting to extrinsic evidence
as to the general meaning of the term “substantially”
standing on its own, we should interpret the claim term
that Aventis did define: “substantially pure.”

     There is no basis for ignoring the intrinsic record and
the presumption that “substantially pure” is a discrete
claim term with a consistent meaning throughout the
patent. Aventis apparently believes that for “substantial-
ly pure” to be construed to have the same meaning each
time it is used in the patent, the patentee would have to
explicitly “link” the purity of the para-CPK intermediate
to that of the end product. But Aventis has it backwards:
If the patentee wanted “substantially pure” to have differ-
ent meanings when applied to different elements, it
needed to explicitly “unlink” them.

                             II

    Aventis’s other arguments are easily disposed of. It is
clear (and essentially undisputed) that “substantially
pure” means “at least 98% pure” when describing end
product. In the prosecution history of the ’703 patent, the
applicant equated substantially pure piperidine deriva-
tive with “a purity level suitable for pharmaceutical use.”
The district court found that “[i]t is essentially undisput-
ed that pharmaceutically acceptable purity is 98%.” The
patentee’s statements made in the course of an interfer-
ence proceeding involving the ’610 patent also support the
district court’s conclusion that the term “substantially
pure,” as used in the ’906 patent and its relatives, means
“at least 98% pure.” In that interference proceeding, the
patentee equated the term “substantially pure” with
“pharmaceutical grade purity” and expressly agreed that
“pharmaceutical grade purity requires an impurity level
no greater than 2%.” The prosecution histories also
support the district court’s conclusion that the required
9                         AVENTIS PHARMA   v. MYLAN PHARMA

purity level referred to purity with respect to all impuri-
ties, not just with respect to a single other component,
such as meta-CPK.

    Aventis argues that this evidence is irrelevant be-
cause it pertains to the purity level of the end product.
But because the patent does not distinguish between the
meaning of “substantially pure” as applied to an end
product and as applied to an intermediate, it follows that
if a “substantially pure [end product]” means a product
that is at least 98% pure with respect to all impurities,
then the same meaning attaches to “substantially pure
[para-CPK].”

    The cases that Aventis cites in support of its position
are unhelpful to it. Aventis cites several cases for the
proposition that the term “substantially” need not have a
strict numerical boundary. E.g., Playtex Prods., Inc. v.
Procter & Gamble Co., 400 F.3d 901, 907 (Fed. Cir. 2005);
Anchor Wall Sys. v. Rockwood Retaining Walls, Inc., 340
F.3d 1298, 1310-11 (Fed. Cir. 2003); Cordis Corp. v.
Medtronic AVE, Inc., 339 F.3d 1352, 1360 (Fed. Cir.
2003); Ecolab, Inc. v. Envirochem, Inc., 264 F.3d 1358,
1366 (Fed. Cir. 2001). Those cases have no application
here, however, because in this case the intrinsic evidence
establishes that the term “substantially pure” was given a
strict numerical meaning, as the district court found.

    In sum, I conclude that “substantially pure” means “at
least 98% purity with respect to all impurities” and that it
has that meaning with respect to both regioisomers and
the end product. I would therefore affirm the district
court’s judgment.