MEDEVA PHARMA SUISSE A.G. et al v. PAR PHARMACEUTICAL, INC. et al
Filing
197
OPINION filed. Signed by Judge Freda L. Wolfson on 6/1/2012. (eaj)
** NOT FOR PUBLICATION **
UNITED STATES DISTRICT COURT
DISTRICT OF NEW JERSEY
____________________________________
:
MEDEVA PHARMA SUISSE A.G.,
:
et al.,
:
:
Plaintiffs, :
:
v.
:
:
PAR PHARMACEUTICAL, INC.,
:
et al.,
:
:
Defendants. :
:
____________________________________:
Civil Action No. 10-cv-4008
OPINION
Plaintiffs Medeva Pharma Suisse A.G. (“Medeva”), Warner Chilcott
Pharmaceuticals, Inc. and Warner Chilcott Company, LLC (“Warner Chilcott,”)
(collectively referred to as “Plaintiffs”) bring this patent infringement action alleging,
inter alia, infringement of U.S. Patent No. 5,541,170 (“the ‘170 patent”) by Defendants
Par Pharmaceutical, Inc. (“Par”) and Emet Pharmaceuticals, LLC (“Emet,” collectively
referred to as “Defendants”) in submitting their Abbreviated New Drug Application
(“ANDA”) to market a generic version of the Asacol® drug product, which is approved
for the treatment of an inflammatory disease of the large intestine. Asacol® is
currently produced by Warner Chilcott and covered by the ’170 patent owned by
Medeva.
Before the Court is the parties’ request that the Court construe the following
terms in dispute within the claims of the ’170 patent: 1) “whereby the dosage form
releases the 5-amino-salicylic acid, salt or ester to the right side of the colon” /
“whereby the 5-amino-salicylic acid is released to the right side of the colon”; 2) “a layer
which is insoluble in gastric juice and in intestinal juice below pH 7 but soluble in
colonic intestinal juice”; and 3) “said solid oral dosage form being coated so as to release
the 5-amino-salicylic acid, salt or ester to the right side of the colon.” A Markman
hearing was held on October 18, 2011.
The Court has considered the written
submissions of the parties, along with the certifications and testimony of Plaintiffs’
expert, Dr. Roland Bodmeier, and Defendants’ expert, Dr. Edmund Elder, Jr.. The
Court shall construe the terms in the context of the asserted claims as set forth herein.
I.
BACKGROUND
In light of the protracted prosecution history relating to the ‘170 patent, and the
parties’ reliance upon various aspects of that history, the Court includes a lengthier
than usual background section in this Opinion. That said, this section provides only
an overview and there are specific aspects of the prosecution history that are
addressed, where relevant, in the body of the Opinion.
A.
The ’170 Patent
The ’170 patent, entitled “Orally Administrable Pharmaceutical Compositions,”
claims certain pharmaceutical compositions that allow selective administration of a
pharmacologically active agent to the large intestine (also known as “the colon”). The
claims of the ’170 patent include Asacol® and its methods of production.
The active ingredient of Asacol® is mesalamine (5-amino-salicylic acid, or
5-ASA). Mesalamine has been used since the 1970s in treating diseases or ailments
2
of the colon, especially ulcerative colitis or Crohn’s disease. Ulcerative colitis begins
at the rectum and then progresses backwards through the colon, in some patients all
the way to the beginning of the ascending colon. Prior to the ‘170 patent invention,
mesalamine was administered in the form of the drug substance sulphasalazine
(“SASP”), a complex drug substance that is broken down to mesalamine and
sulphapyridine by colonic bacteria. Although SASP was effective, patients often
suffered serious side effects. Realizing that the sulphapyridine was responsible for
such side effects, pharmaceutical companies directed efforts toward developing a way
of delivering mesalamine to the colon that retained SASP’s effectiveness but avoided
its side effects. However, the prior art to the ‘170 patent did not achieve such a goal,
and orally administered dosage forms were generally absorbed into the blood stream
in the stomach or small intestine before reaching the colon.
The ‘170 patent describes a solid oral dosage form containing mesalamine,
coated with an anionic polymer (or polymers) designed to remain intact until reaching
the colon, and to release the mesalamine to the colon without substantial leaching
before reaching the colon. Based in part on the fact that the pH in the human
gastrointestinal tract increases from the stomach to the colon, by which point the pH
reaches about 7, the inventors found a formula for the layer that is insoluable below
pH 7, but soluble above pH 7. Once the dosage form reaches the colon, the coating
layer begins to dissolve, and accordingly mesalamine is administered to the colon.
B.
Prosecution History
On July 28, 1982, following a clinical trial demonstrating that the claimed
3
formulation was as effective as SASP in treating ulcerative colitis, the inventors filed
an application for a U.S. patent (No. 82/000235).
After several continuation
applications (No. 06/482,331, No. 06/735,727, No. 07/584,386, No. 07/858,449 and No.
08/032,167), the inventors filed a divisional application (No. 08/401,696) on March 10,
1995, which ultimately led to the issuance of the ‘170 patent on July 30, 1996.
Meanwhile, the patent application of No.08/032,167 was followed by another
continuation application (No.08/448,300), for which the Patent Office issued U.S.
Patent No. 5,541,171 (“the ‘171 patent”).1 In filing the divisional application, which
separated out the claims ultimately incorporated into the ’170 patent, the patentees
sought to patent broader claims than those ultimately incorporated into the ‘171
patent.
In short, the ’170 and ‘171 patents flow from the same earlier continuation
applications. The following chart illustrates the history of these related patents.
[next page]
1
Even though Plaintiffs made no claim that Defendants’ ANDA infringed
upon the ‘171 patent, Defendants filed a counterclaim for declaratory judgment
regarding the validity of the ‘171 patent. This Court dismissed it on the ground that
Defendants lack standing to bring the counterclaim based upon Plaintiffs’ offering of
a covenant not to sue Defendants on the ‘171 patent. Medeva Pharma Suisse A.G. v.
Par Pharm., Inc., 774 F.Supp.2d 691, 699 (D.N.J. 2011), aff'd, 2012 U.S. App. LEXIS
1516 (Fed. Cir. Jan. 25, 2012).
4
The prosecution history for the ’170 patent, and the related ‘171 patent, is
extensive, spanning over fourteen years. As noted above, the use of 5-ASA topically on
the colon was a familiar treatment; it was the patentees’ ability to ensure that the
treatment did not leach out before reaching the colon that made their invention unique.
Hence, throughout the prosecution of the patent, the patentees spent significant time
5
distinguishing their formulation from the prior art. In this connection, the patentees
further emphasized the high organ specificity of their coating and dosage form, and
that the mesalamine was “dumped” into the colon, rather than consistently released
in small amounts prior to, throughout, and following the colon.
The several
continuation applications were occasioned by the patentees’ failure to convince a given
examiner that their invention was not obvious to one familiar with the prior art.
Through their perseverance, the patentees were ultimately able to convince the
examiners that their patents should be issued.
There are three types of prior art distinguished by the patentees throughout the
prosecution history that are relevant here. One prior art was the use of a coating
comprised of mixtures of Eudragit S & Eudragit L, in certain thicknesses, which
thickness was insufficient to ensure that the 5-ASA did not leach out before reaching
the colon. Contrary to the prior art, the patentees contended that their coating was
thicker and, consequently, did not dissolve too early in the intestinal tract. In this
connection, the patentees also noted that they used coatings comprised only of
Eudragit S, as opposed to both S & L, along with other polymers.
Another prior art was the use of a resin in the coating formulation that effected
a time release-based delivery. Rather than employing a time-release carrier system
for delivering the drug, the patentees’ formulation was pH-dependent; the patentees’
coating would not dissolve until it reached the area of the intestines that contains pH
7 fluids. The patentees further argued that a pH-based carrier system is more reliable
because release of the drug from a time-release system may vary from two to five hours
6
and, thereby, release too early during the digestive process before reaching the colon.
Finally, the patentees distinguished all prior oral administrations of 5-ASA as
not specified to prevent release of 5-ASA before reaching the colon.
C.
Comparing the ’170 and ‘171 patents
As noted, the ‘170 and ‘171 patents share the same parent applications, those
filed from 1982 through 1993. However, per the divisional application filed in 1995,
the patentees split their application into two. Divisional Application No. 08/401,696
became the application for what was ultimately issued as the ’170 patent, and
Continuing Application No. 08/448,300 became the application for what was ultimately
issued as the ‘171 patent.
Generally, divisional applications are submitted by applicants where the PTO
has imposed a restriction requirement on the applicants’ original application. “An
examiner enters a restriction requirement when he determines that the application
includes claims to independent and distinct inventions.” 4A-12 Chisum on Patents §
12.04; see 35 U.S.C. § 121 (“If two or more independent and distinct inventions are
claimed in one application, the Director may require the application to be restricted to
one of the inventions.”). Thereafter, the applicant must elect one of the inventions to
pursue. See 37 C.F.R. § 1.142. After the applicant has elected one of the inventions,
the patent examiner will withdraw from further consideration all claims for the
nonelected inventions. 4A-12 Chisum on Patents § 12.04. An applicant who wishes to
pursue what was withdrawn “may file a divisional application claiming the nonelected
inventions ....” Id.
7
A key difference between the ‘171 patent and the ’170 patent here is that the
former expressly excludes coating mixtures of Eudragit S & Eudragit L whereas the
latter does not.
Further, as noted, the patentees sought broader claims in the
divisional application that resulted in the ’170 patent.
D.
Disputed Claims
The parties present three disputed terms for construction in claims1, 6 and 7 of
the ‘170 Patent. The claim language reads:2
Claim 1
1.
An orally administrable pharmaceutical composition for selectively
administering 5-amino-salicylic acid, or pharmaceutically acceptable salt or ester
thereof, to the large intestine, comprising a solid oral dosage form containing a
pharmaceutically effective amount for the treatment of ulcerative colitis or Crohn’s
disease of the colon of said 5-amino-salicylic acid, salt or ester, said solid oral dosage
form being coated with a layer which is insoluble in gastric juice and in intestinal juice
below pH 7 but soluble in colonic intestinal juice, whereby the dosage form releases the
5-amino-salicylic-acid, salt or ester to the right side of the colon.
Claim 6
6.
A method for treating ulcerative colitis or Crohn’s disease of the colon
comprising orally administering to a person suffering therefrom the composition of
claim 1 whereby the 5-amino-salicyclic acid is released to the right side of the colon.
Claim 7
7.
An orally administrable pharmaceutical composition for selectively
administering 5-amino-salicylic acid, or pharmaceutically acceptable salt or ester
thereof, to the large intestine, comprising a solid oral dosage form containing a
pharmaceutically effective amount for the treatment of ulcerative colitis or Crohn's
disease of the colon of said 5-amino-salicylic acid, salt or ester, said solid oral dosage
form being coated so as to release the 5-amino-salicylic acid, salt or ester to the right
side of the colon.
2
The disputed terms are highlighted.
8
To understand the parties’ proposed constructions, a basic schematic of the
gastrointestinal tract is useful.
Bodomeier Decl. dated Jun. 2, 2011 at ¶ 11.
As this schematic illustrates, the ileum precedes the cecum (also referred to as
the caecum) and the ascending colon. Both parties agree that, in common parlance,
“colon” refers to the area beginning with the ascending colon (or “right side of the
colon”) and does not include the ileum. This area, the ascending colon, is also referred
to by the parties as the “large intestine.” One of the parties’ key claim construction
disputes is whether the patentees taught that their formulation of 5-ASA would release
in both the ileum and the ascending colon. To be clear, the parties refer in their
proposed constructions specifically to the distal ileum (or terminal ileum), which is the
latter most part of the ileum adjacent to the cecum. The patentees used distal ileum
9
and terminal ileum interchangeably throughout the prosecution history. For ease of
reference, the Court will use the term distal ileum except when quoting prosecution
history statements, the parties’ briefs, or proposed constructions that refer to the
terminal ileum.
The parties’ proposed constructions of the disputed terms are as follows:
Disputed Terms
Plaintiffs’ Construction
A layer which is insoluble in gastric
juice and in intestinal juice below
pH 7 but soluble in colonic
intestinal juice (Claim 1)
The dosage form is coated
with at least one layer that
has sufficient thickness so
that the coating does not
fully dissolve or
disintegrate in gastric juice
and in intestinal juice
below pH 7, but does
dissolve or disintegrate in
colonic intestinal juice.
Whereby the dosage form releases the Substantially all of the drug
5-amino-salicylic-acid, salt or ester to leaves the dosage form in
the right side of the colon (Claim 1) the distal part of the small
intestine or the ascending
colon.
Defendants’ Construction
None of the layer dissolves
(i.e., the layer is insoluble)
in aqueous medium below
pH 7 but the layer does
dissolve below pH 7.5.
This excludes layers
containing mixtures of
Eudragit S and Eudragit L.
The coating reliably releases
all of the active ingredient
contained in the dosage form
to the right side of the colon
(i.e., the ascending colon,
and not the terminal ileum).
Whereby the 5-amino-salicylic-acid is
released to the right side of the colon
(Claim 6)
(same)
(same)
Said oral dosage form being coated so
as to release the 5-amino-salicylicacid, salt or ester to the right side of
the colon (Claim 7)
Substantially all of the drug
leaves the dosage form in
the distal part of the small
intestine or the ascending
colon.
The coating is insoluble
below pH 7, i.e. Eudragit S,
and thereby reliably
releases all of the active
ingredient contained in the
dosage form to the right
side of the colon (i.e., the
ascending colon, and not
the terminal ileum).
10
II.
LEGAL STANDARDS
A.
General Claim Construction Standard
Claims define the scope of the inventor’s right to exclude. Phillips v. AWH
Corp., 415 F.3d 1303, 1312 (Fed. Cir. 2005). Claim construction determines the
correct claim scope, and is a determination exclusively for the court as a matter of
law. Markman v. Westview Instruments, Inc., 52 F.3d 967, 978-79 (Fed. Cir. 1995)
(en banc). Indeed, the court can only interpret claims, and “can neither broaden nor
narrow claims to give the patentee something different than what it has set forth” in
the specification. E.I. Du Pont de Nemours v. Phillips Petroleum Co., 849 F.2d 1430,
1433 (Fed. Cir. 1988).
This interpretive analysis begins with the language of the claims, which is to
be read and understood as it would be by a person of ordinary skill in the art. Dow
Chem. Co. v. Sumitomo Chem. Co., 257 F.3d 1364, 1372 (Fed. Cir. 2001); see also
Markman, 52 F.3d at 986 (“The focus [in construing disputed terms in claim
language] is on the objective test of what one of ordinary skill in the art at the time
of invention would have understood the terms to mean”); Phillips, 415 F.3d at
1312-13. In construing the claims, the court may examine both intrinsic evidence
(e.g., the patent, its claims, the specification and prosecution history) and extrinsic
evidence (e.g., expert reports, testimony and anything else). Pitney Bowes, Inc. v.
Hewlett-Packard Co., 182 F.3d 1298, 1309 (Fed. Cir. 1999). However, claims may not
be construed with reference to the accused device, which means that the court may
11
not construe a claim to fit the dimensions of the accused device, thus to prejudice the
claim construction by “excluding or including specific features of the accused device.”
Wilson Sporting Goods Co. v. Hillerich & Bradsby Co., 442 F.3d 1322, 1330 (Fed. Cir.
2006). Nevertheless, the knowledge of the accused device before or during claim
construction is not only permissible, but also necessary to claim construction because
it “supplies the parameters and scope of the infringement analysis.” Id. at 1330-31;
Lava Trading Inc. v. Sonic Trading Mgmt., 445 F.3d 1348, 1350 (Fed. Cir. 2006).
In interpreting the disputed terms, it is well settled that the Court should look
first to the intrinsic evidence. Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576,
1582 (Fed. Cir. 1996). Generally, words in patent claims are given their “ordinary
and accustomed meaning as understood by one of ordinary skill in the art” at the
priority date of the patent application. Dow Chem., 257 F.3d at 1372; K-2 Corp. v.
Salomon S.A., 191 F.3d 1356, 1362 (Fed. Cir. 1999). The claims must be construed
objectively in the context of both the particular claim and the entire patent because
“the claims themselves provide substantial guidance as to the meaning of particular
claim terms,” and claim terms are normally used consistently throughout the patent.
Phillips, 415 F.3d at 1313-14.
Moreover, courts are instructed to look to the specification, which is a written
description of the invention. “[C]laims ‘must be read in view of the specification, of
which they are a part.’” Id. at 1315 (quoting Markman, 52 F.3d at 979). Indeed, the
specification is perhaps “the single best guide to the meaning of a claim term” due to
its statutory requirements of being in “full, clear, concise, and exact terms.” Id. at
12
1316; see 35 U.S.C. §112. “The specification acts as a dictionary when it expressly”
or implicitly defines terms used in the claims. Markman, 52 F.3d at 979. Thus, it
effectively limits the scope of the claim.
On Demand Mach. Corp. v. Ingram
Industries, Inc., 442 F.3d 1331, 1340 (Fed. Cir. 2006). Due to its nature, “the
specification ‘is always highly relevant to the claim construction analysis. Usually
it is dispositive.” Id. (quoting Vitronics Corp., 90 F.3d at 1582).
Extrinsic evidence includes all evidence external to the patent and prosecution
history, i.e., expert and inventor testimonies, dictionaries, and learned treaties.
Markman, 52 F.3d at 980. It is considered only where the intrinsic evidence does not
provide a sufficient description to resolve ambiguities in the scope of the claim. See
Vitronics, 90 F.3d at 1583; Johnson Worldwide Assocs. v. Zebco Corp., 175 F.3d 985,
989 (Fed. Cir. 1999). However, the Federal Circuit cautioned, in Phillips, that
dictionary definitions should not be used to interpret patent claim terms in a manner
that is divorced from the context and description of the invention in the specification.
Phillips, 415 F.3d at 1321. The Phillips court reasoned that because of the nature of
the patent claims, the dictionary definitions, as extrinsic evidence, are usually less
reliable than the patent documents themselves in establishing the ordinary meaning
of a claim term. Id. at 1314; Toro Co. v. White Consol. Indus., 199 F.3d 1295, 1299
(Fed. Cir. 1999). Ultimately, extrinsic evidence cannot be used to vary or contradict
claim terms when their meanings are discernible from intrinsic evidence. C. R. Bird,
Inc. v. U.S. Surgical Corp., 388 F.3d 858, 862 (Fed. Cir. 2004).
B.
Disclaimers and Disavowals
13
“[I]n certain cases, the specification may reveal an intentional disclaimer, or
disavowal, of claim scope by the inventor.” Ventana Medical Systems, Inc. v. Biogenex
Laboratories, Inc., 473 F.3d 1173, 1181 (Fed. Cir. 2006) (quoting Phillips, 415 F.3d
at 1316) (internal citations omitted). In such cases, the Federal Circuit interprets the
claim more narrowly than it otherwise would in order to give effect to the patentee’s
intent to disavow a broader claim scope. Id. (citing Honeywell Int'l, Inc. v. ITT
Indus., Inc., 452 F.3d 1312, 1319-20 (Fed. Cir. 2006); SciMed Life Sys., Inc. v.
Advanced Cardiovascular Sys., Inc., 242 F.3d 1337, 1342-44 (Fed. Cir. 2001).
However, pointing solely to “general statements by the [patentee] indicating
that the invention is intended to improve upon prior art” will not demonstrate that
the patentee intended to “disclaim every feature of every prior art device discussed
in the ‘BACKGROUND ART’ section of the patent.” Id. See also Thorner v. Sony
Computer Entertainment America LLC, 669 F.3d 1362 (Fed. Cir. 2012) (“Mere
criticism of a particular embodiment encompassed in the plain meaning of a claim
term is not sufficient to rise to the level of clear disavowal.”) (quoting Epistar Corp.
v. Int'l Trade Comm'n, 566 F.3d 1321, 1335 (Fed. Cir. 2009)).
Moreover, the Federal Circuit has found it “particularly important not to limit
claim scope based on statements made during prosecution ‘[a]bsent a clear disavowal
or contrary definition.” Digital-Vending Services Intern., LLC v. University of
Phoenix, Inc., 672 F.3d 1270, 1273 (Fed. Cir. 2012) (citing August Tech. Corp. v.
Camtek, Ltd., 655 F.3d 1278, 1286 (Fed. Cir. 2011) (quoting Home Diagnostics, Inc.
v. LifeScan, Inc., 381 F.3d 1352, 1358 (Fed. Cir. 2004)). The reason for such a
14
stringent rule is “because the prosecution history represents an ongoing negotiation
between the PTO and the applicant, rather than the final product of that negotiation,
it often lacks the clarity of the specification and thus is less useful for claim
construction purposes.” Id. (quoting Phillips, 415 F.3d at 1317).
C.
Related Applications
Generally, “statements made by the inventor during continued prosecution of
a related patent application can, in some circumstances, be relevant to claim
construction.” Ventana, 473 F.3d at 1184 (citing Microsoft Corp. v. Multi-Tech Sys.,
Inc., 357 F.3d 1340, 1349 (Fed. Cir. 2004)). This is particularly so where “the
prosecution history of one patent is relevant to an understanding of the scope of a
common term in a second patent stemming from the same parent application.” MultiTech, 357 F.3d at 1349. Similar to statements made by the patentee during the
prosecution of an ancestor application, “statements made during the continued
prosecution of a sibling application may inform the meaning of the claim language by
demonstrating how the inventor understood the invention.” Ventana, 473 F.3d at
1184 (citing Phillips, 415 F.3d at 1317). Moreover, the “prosecution history of a
related patent application may inform construction of a claim term, when the two
applications are directed to the same subject matter and a clear disavowal or
disclaimer is made during prosecution of the related application.” TIP Sys., LLC v.
Phillips & Brooks/Gladwin, Inc., 529 F.3d 1364, 1371 (Fed. Cir. 2008).
Prosecution history estoppel applies with equal force to divisional applications.
See Desper Prods., Inc. v. QSound Labs, Inc., 157 F.3d 1325, 1339 n. 6 (Fed. Cir.
15
1998) (relying on common parent application to construe claims in both a divisional
and a related application). However, “[w]hen the applicant is seeking different claims
in a divisional application, estoppel generally does not arise from the prosecution of
the parent.” Biogen, Inc. v. Berlex Laboratories, Inc., 318 F.3d 1132, 1140 (Fed. Cir.
2003).
III.
DISCUSSION
The parties’ claim construction arguments relate to two claim terms: the
“release to the right side of the colon” language found in claims1, 6, and 7; and the
“insoluble in gastric juice” language found in claim 1. In addition, Defendants further
argue, via the doctrine of prosecutory estoppel, that the patentees disclaimed
mixtures of Eudragit S and Eudragit L. Finally, Defendants contend that a pH
limitation should be read into claim 7 although that claim includes no such express
limitation. I address each of these issues in turn.
A.
Releasing “to the right side of the colon”
Each of the disputed claims speaks of releasing 5-ASA “to the right side of the
colon.” As explained above, 5-ASA must be applied topically, thus, the precise
placement of the formulation onto the colon’s surface is central to the patentees’
invention. In this connection, the parties dispute whether “to the right side of the
colon” should be construed to mean releasing within the distal ileum or the ascending
colon (Plaintiffs’ view) or, alternatively, to release only within the ascending colon
and not within the distal ileum (Defendants’ view). In addition, the parties dispute
what amount of the drug must be released. Plaintiffs construes the claim language
16
to mean that “substantially all” (at least 80%) of the drug must be released whereas
Defendants argue that “all” (near 100%) of the drug must be released to the right side
of the colon.
The parties proposed constructions are as follows:
Claim Language
Plaintiffs’ Construction
Defendants’ Construction
Whereby the dosage form
releases the 5-amino-salicylic
acid, salt or ester to the right
side of the colon (Claim 1) /
Whereby the 5-amino-salicylic
acid is released to the right side
of the colon (Claim 6)/ Said
oral dosage form being coated
so as to release the 5-aminosalicylic-acid, salt or ester to
the right side of the colon
(Claim 7)
Substantially all of the
drug leaves the dosage
form in the distal part of
the small intestine or the
ascending colon.
The coating reliably releases all
of the active ingredient contained
in the dosage form to the right
side of the colon (i.e., the
ascending colon, and not the
terminal ileum).
1.
Distal Ileum
Defendants argue that their construction comports with the ordinary meaning
of “right side of the colon.” First, they note that the right side of the colon (also
known as ascending colon) is a part of the large intestine, and therefore the small
intestine is not included by definition. Furthermore, because the patentees never
expressly defined “the colon” to include the distal part of the small intestine,
Defendants contend that Plaintiffs’ construction is inconsistent with the claim
language. Citing Merck & Co. v. Teva Pharms. USA, 395 F.3d 1364, 1370 (Fed. Cir.
2005), for the proposition that “[w]hen a patentee acts as his own lexicographer in
redefining the meaning of particular claim terms away from their ordinary meaning,
17
he must clearly express that intent in the written description,” Defendants argue that
the patentees did not clearly express an intent to redefine the phrase “right side of
the colon.”
In support of their argument that the patentees did not intend release in the
distal ileum to be a part of the invention, Defendants point to an example in the
specification. In Example IV in the specification, six capsules were given to each of
six patients (36 capsules in total) and their integrity was tracked over time via X-ray
analysis. Four of the capsules broke in the distal ileum and 23 broke at the colon.
According to Defendants, the results of the Example show that the patentees
considered the invention exemplified by the 23 capsules that “remained intact after
oral ingestion until they reached the right side of the colon when the capsule broke
releasing its contents,” and not the four capsules that broke in the distal ileum. ’170
patent, col. 7 at 16-19.
By contrast, Plaintiffs contend that the intrinsic evidence confirms that the
claim limitation of “release to the right side of the colon” encompasses liberation of
the drug in the distal portion of the small intestine. For example,
•
Example IV—the same example relied upon by Plaintiffs— reports that the
capsules “remained intact in the stomach and proximal small bowel [upper
small intestine]” and then broke either in the “distal ileum” or the colon. ’170
patent col. 7 at 3-7.
•
A September 26, 1984 Amendment explains that the patentees’ preference for
a coating thickness between 60 and 160 microns as providing for a coating
“which would reliably break in the terminal ileum or in the proximal large
intestine (ascending caecum and ascending colon usually).”
18
•
A March 14, 1988 Response states that “[t]his unit dosage form [of the
invention] has been developed to carry the [mesalamine] to the last portion of
the small intestine or the first portion of the colon before the coating
disintegrates or dissolves, in order to provide an effective dose of [mesalamine]
to the colon for the treatment of ulcerative colitis or Crohn's disease therein.”
•
A November 17, 1995 Responsive Amendment states that “[t]he composition of
the claimed invention is embodied in the product Asacol®” and then cites
literature showing Asacol®, an embodiment of the ’170 patent, “break[ing] up
in the terminal ileum or ascending colon.”
Plaintiffs’ Opening Br. at 12-13 (citations omitted).
In addition, Plaintiffs argue that the intrinsic evidence also describes the
preferred embodiment of the claims—a solid oral dosage form coated with a thick
Eudragit S coating—as releasing the drug in the distal ileum in order to provide
therapy throughout the colon. Because Defendants construe claims to exclude release
in the distal ileum, Plaintiffs reason that it is contrary to the intrinsic evidence, and
would improperly exclude the preferred embodiment from the claims. As such,
Defendants’ construction must be, according to Plaintiffs, rejected, because “[a] claim
interpretation that reads out a preferred embodiment is rarely, if ever, correct and
would require highly persuasive evidentiary support.” Id. at 13 (quoting Virtonics
Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1583 (Fed. Cir. 1996)).
More importantly, Plaintiffs emphasize that Defendants’ construction is clearly
contradicted by the expressed definition of the claim term provided by the inventors
in connection with a related application. Plaintiffs note that in a continuation
application (the ’300 application) that ultimately led to issuance of the ‘171 patent,
the patentees expressly stated that “the claim limitations of remaining ‘intact until
19
it reaches the colon’ and ‘release to the right side of the colon’ embrace breaking up
in the terminal ileum or ascending colon and releasing in the distal part of the small
intestine.” Id. at 14 (quoting Ainsworth Ex. F at 7). Accordingly, Plaintiffs maintain
that Defendants’ proposal to exclude such release from the claims is inconsistent with
the claim language and the intrinsic evidence.
Furthermore, Plaintiffs cite to the declaration of their expert witness, Dr.
Bodmeier.
In his declaration, Dr. Bodmeier explained that because coating
dissolution and tablet disintegration are not instantaneous events, it may be
preferable to design dosage form to disintegrate shortly before entry into the right
side of the colon in the distal portion of the small intestine. Bodmeier Decl., ¶ 29.
Because the best way to deliver the drug to the very beginning of the right side of the
colon (around the cacum) may be to release the drug near the end of the small
intestine (e.g., in the distal ileum), Plaintiffs claim that a skilled artisan would
understand that release to the right side of the colon includes release in the distal
ileum .
Because the parties do not dispute that the ordinary and customary meaning
of the “right side of the colon” does not include the distal part of the small intestine,
the issue before the Court is whether the patentees clearly expressed their intention
in the patent or prosecution history to either: (a) include the distal part of the small
intestine in the definition of “right side of the colon;” or (b) by claiming that the drug
will release “to” the right side of the colon, expressed their intention that the drug
20
release in the distal ileum in order to facilitate topical application in the ascending
colon, as Dr. Bodomeier suggests.
As an initial matter, I reject the argument that the patentees acted as their own
lexicographer by specially defining “right side of the colon” in the specification or the
prosecution history. There is no language in the specification that can be read as
clearly setting forth a special definition of either colon or “right side of the colon.”
Indeed, the only reference to the distal ileum in the specification is in Example IV,
and that example distinguishes between the distal ileum and the colon: “In a few
patients occasional capsules broke in the distal ileum (4 of 36) but after 12 hours 32
capsules had reached the colon and of these, 23 had broken at this site.” ’170 Patent,
col. 7 at 4-7 (emphasis added). See also File History, 06/482,331 App., Sept. 26, 1984
Amendment at 9 (Ainsworth Decl., Exh. J at WC373) (“[T]he coating would reliably
break in the terminal ileum or in the proximal large intestine (ascending caecum and
ascending colon usually).”) (emphasis added).
However, the claim language envisions an initial breaking or disintegration of
the coating layer in the distal ileum so as to release the 5-ASA in the colon. While,
on the one hand, the patentees describe the invention in the specification as
“remain[ing] intact until it reaches the colon,” see e.g., ‘170 Patent, col. 4 at 20; id. at
4:30; id. at 4:63, the broadly worded claim language of releasing “to” the colon
encompasses the initial dissolution in the distal ileum in order to ensure that the
drug is topically applied on the colon’s surface. Moreover, the Federal Circuit has
repeatedly held it inappropriate to read limitations from the specification into the
21
claim. See e.g., Thorner, 669 F.3d at 1366 (“We do not read limitations from the
specification into claims ....”); Phillips, 415 F.3d at 1315, 1323 (“The claims are read
in context with the specification, but limitations from the specification should not be
read into the claims.”). And, “[i]t is the claims that define the metes and bounds of the
patentee’s invention.” Thorner, 669 F.3d at 1367.
It is true that for all the embodiments of the invention discussed in the
specification, it is anticipated that the “dissolution or disintegration [will] not occur
until entry of the coated dosage form into the colon.” Id. col. 4 at 1-3. Nevertheless,
“[i]t is . . . not enough that the only embodiments, or all of the embodiments, contain
a particular limitation.” Thorner, 669 F.3d at 1366. See also Kara Technology Inc.
v. Stamps.com Inc., 582 F.3d 1341 (Fed. Cir. 2009) (“[W]e have expressly rejected the
contention that if a patent describes only a single embodiment, the claims of the
patent must be construed as being limited to that embodiment.”) For a limitation to
be imported from the specification into a claim, the specification must describe the
“present invention” or otherwise make explicit that all contemplated embodiments
of the claim contain the limitation. Id. Indeed, this was the case in SciMed, 242 F.3d
at 1341, a case relied upon by Defendants. Unlike SciMed, the specification here
makes no pronouncement that all contemplated embodiments will break or release
in the colon.
In addition, Example IV in the specification supports my construction of the
“release to the right side of the colon” language. As noted, in that example, the
patentees described the capsules as occasionally breaking “in the distal ileum ....”
22
’170 Patent, col. 7 at 5. I note, however, that the Example IV language suggests that
occasional rather than frequent breaking in the distal ileum was contemplated.
The prosecution history of the ’170 patent further supports my construction.
There is language in the early prosecution history of both the ’170 and ‘171 patents,
before the patent applications were divided, that embraces release in the distal ileum.
During prosecution of the ’331 application, in 1984, the patentees stated that they
“obtained a consistent behavior of the coating would reliably break in the terminal
ileum or in the proximal large intestine (ascending caecum and ascending colon
usually).” File History, 06/482,331 App., Sept. 26, 1984 Amendment at 9 (Ainsworth
Decl., Exh. J at WC373). Similarly, in connection with the ’727 application, the
patentees stated that the “dosage form has been developed to carry the 5-ASA to the
last portion of the small intestine or first portion of the colon, before the coating
disintegrates or dissolves ....” File History, 06/737,727 App., Mar. 14, 1988 Response
and Presentation of Evidence Under Rule 12 at 3 (Ainsworth Decl., Exh. K at
WC446).
There is also language embracing initial dissolution in the distal ileum in the
divisional application that ultimately resulted in the issuance of the ‘170 patent,
although that language refers specifically to the preferred embodiment Asacol®. In
the prosecution of that application, the patentees stated that Asacol® “has been
shown to break up in the terminal ileum or ascending colon,” File History, 06/401,696
App., Nov. 17, 1995 Responsive Amendment at 4-5 (Ainsworth Decl., Exh. E at
23
WC132-33), and that it “dissolves in the terminal ileum.”
Id., Mar. 13, 1996
Responsive Amendment at 4 (Ainsworth Decl., Exh. O at WC180).3
Read together, these statements from the prosecution history support a
construction of the “release to the right side of the colon” claim language that includes
release in the distal ileum.4 That the patentees also intermittently used the phrase
“release . . . in the colon” to describe the drug’s release profile in parts of the
specification and prosecution history does not alter my construction. For example,
Defendants point to language in the specification distinguishing prior art as “not
provid[ing] for release of 5-ASA only in the colon.”
‘170 patent, col. 3: 59-60
(emphasis added). While this isolated statement might suggest that the patentees
used “in the colon” and “to the colon” interchangeably, by reading the sum of the
prosecution history it is clear that their focus was topical application of the 5-ASA to
the colon wall whether the dosage form began to dissolve in the distal ileum or the
ascending colon.
3
Defendants argued at oral argument that Asacol® is not a preferred
embodiment because it did not exist at the time of the original 1984 patent application.
Even so, Asacol® utilizes a coating of neat Eudragit S, which Defendants do not contest
falls within the bounds of the claims. Moreover, Defendants appear to contend that the
’170 patent claims should be limited to Eudragit S formulations by arguing that the
patentees disavowed mixtures of Eudragit S and Eudragit L.
4
Plaintiffs further point to a clear and unequivocal statement regarding
release to the right side of the colon made during the post-division related patent
application (the ’300 application) for the ‘171 patent. In light of the aforesaid
statements made in connection with the ‘170 patent prosecution, I need not rely on this
statement in the related Patent’s’171 patent file history.
24
The Court does not wholesale adopt Plaintiffs’ construction, however.
In
construing the claims, “[t]he judge’s task is not to decide which of the adversaries is
correct. Instead, the judge must independently assess the claims, the specification,
and if necessary the prosecution history, and relevant extrinsic evidence, and declare
the meaning of the claims.” Exxon Chem. Patents, Inc. v. Lubrizol Corp., 64 F.3d
1553, 1556 (Fed. Cir. 1995); MEMS Technology Berhad v. International Trade Com'n,
447 Fed.Appx. 142, 153 (Fed. Cir. Jun. 3, 2011) (same). Following that dictate here,
I adopt a slightly more constrained construction.
Plaintiffs’ proposed construction is: “Substantially all of the drug leaves the
dosage form in the distal part of the small intestine or the ascending colon.” The
problem with this construction is that it fails to take into account, as reflected by a
careful reading of claim language, specification, and prosecution history, that the
patentees contemplated that the drug would most often release in the colon and that,
much less often, the drug would begin to leave the dosage from while still in the distal
ileum. Moreover, Plaintiffs’ construction also fails to take into account that the
prosecution history statements focus on the dissolution beginning in the distal ileum
so that the 5-ASA leaves the dosage form in the colon. The Court appreciates that the
invention’s function in the body is not so precise that the dosage form will never
break or begin to release in the distal ileum. Nevertheless, the prosecution history
strongly suggests that the invention was intended to primarily break and/or release
in the colon even where some dissolution or disintegration of the coating began in the
distal ileum.
25
Also supporting my view is that the patentees repeatedly sought to distinguish
the extensive prior art by focusing on the invention’s tendency to release much later
in the digestive system than the prior art. In the specification, for example, the
patentees distinguish prior art using various coating materials on 5-ASA capsules as
unable “to prevent release of 5-ASA until the colon.” ‘170 patent, col. 3:23-25
(emphasis added). See also id. at 3:57-60 (distinguishing time-release capsules as not
providing for “reliable release of 5-ASA only in the colon) (emphasis added). Most
notably, after distinguishing additional prior art based on the use of granules versus
a capsule, and the thickness of the coating used, the specification describes the
invention as follows:
The Inventors have now found that 5-ASA reliably can be
administered specifically to the large intestine, especially
the colon, by simply coating a solid oral dosage form with a
sufficient thickness of a partly methyl esterified
methylacrylic acid polymer which does not dissolve in
aqueous medium below pH 7 but does dissolve below pH 7.5.
This carrier system differs from those previously disclosed
in relation to 5-ASA in that dissolution or disintegration
does not occur until entry of the coated dosage form into the
colon. In particular, there is substantially no leaching out
of the 5-ASA downstream of the colon in the normal patient.
Id., col. 3:61 - 4:4 (emphasis added). By distinguishing prior art as unable to reliably
dissolve in the colon, without leaching out downstream of the colon, the patentees
contemplated that, on most occasions, the drug would break up in the colon and not
the distal ileum. The patentees’ use of the modifiers “reliably,” as in the “5-ASA
reliably can be administered specifically to the large intestine,” and “substantially,”
as in “there is substantially no leaching out . . . downstream,” further support my
26
construction that the drug form only occasionally begins dissolution prior to entering
the ascending colon.
Moreover, the specification emphasizes the “high organ
specificity” of the “present invention,” id., col. 5:50-52, which further clarifies that the
dosage form is designed to most often begin dissolution and/or break in the ascending
colon.
Finally, the Court has reviewed the extensive, fourteen-year prosecution history
of the ‘170 patent. While it would take too many pages to recount the history in more
detail here, the Court notes that much of the file is spent distinguishing the prior art
on fine points and defending the patentees’ contention—following multiple
rejections—that the invention reliably releases in a manner that ensures topical
delivery to the colon. There are smatterings of phrases throughout the history that
reference release of the drug in the terminal or distal ileum, discussed infra, however,
those statements are farther and fewer between than Plaintiffs suggest. In reading
the file wrapper as a whole, one is left with the firm impression that the patentees
did not anticipate the drug often or regularly dissolving or releasing in the distal
ileum.5 Cf. Computer Docking Station Corp. v. Dell, Inc., 519 F.3d 1366, 1379 (Fed.
Cir. 2008) (explaining that the “totality of the prosecution history informs the
disavowal inquiry”) (quoting Rheox, Inc. v. Entact, Inc., 276 F.3d 1319, 1326 (Fed.
Cir. 2002)) (internal quotation marks omitted). Accordingly, the Court’s construction
5
In this regard, the Court notes that the parties did not provide the Court
with the entire file wrapper for the ‘170 patent perhaps due to the lengthy prosecution
period. The Court reviewed those portions provided by the parties.
27
(set forth below) will take into account the limited circumstances in which the
patentees envisioned the dosage form beginning to dissolve or break in the distal
ileum. The construction will further take into account that the drug will not be
released prior to reaching the distal ileum. In my view, this sort of construction best
reflects the high organ specificity of the invention and the patentee’s focus on
“dumping” the drug into the colon for topical treatment.
2.
The amount to be released
I adopt Plaintiffs’ proposed construction that “substantially all” as opposed to
“all” of the 5-ASA must be released in the colon.6 Defendants acknowledged at oral
argument that the claim language contemplates less than 100% of the drug being
released in the colon. However, Defendants maintain that the amount of the release
has to be close to that percentage. TR 71:14-19.
Defendants further contend that release must reliably reach near 100% release
to the right side of the colon. Defendants’ argument relies on language in the patent
and the prosecution history, in which the patentees frequently use the term “reliable”
to describe the administration of the 5-ASA. Defendants’ Opening Br. at 17-18 (citing
‘170 patent col. 3 at 61-66) (“The Inventors have now found that 5-ASA reliably can
be administered specifically to the large intestine....”); Id., col. 3 at 57-60
(distinguishing prior art that “does not provide for reliable release of 5-ASA only in
6
While the parties’ proposed constructions refer to the 5-ASA as “the drug”
(Plaintiffs’ Construction) or “the active ingredient” (Defendants’ construction), I
consider their alternate descriptions to be distinctions without a difference because the
5-ASA is the active ingredient (drug) in the invention.
28
the colon”); File History, 08/032,167 App., Nov. 10, 1994 Response to Final Rejection
at 3 (Koh Decl., Ex. Y at WC684) (same). See also File History, 06/735,727 App., Jul.
11, 1988 Appeal Brief at 5 (Koh Decl., Ex. S at WC474) (“Applicants have discovered
that 5-ASA can be reliably administered specifically to the large intestine, and
especially the colon ....”). Based on the frequent usage of the term “reliable” in this
fashion, Defendants reason that it is not sufficient that an occasional tablet
arbitrarily releases all of its contents in the right side of the colon, but the dosage
form must “reliably,” i.e., almost always, release all of its contents in the colon.
Defendants’ Opening Br. at 18.
By contrast, Plaintiffs propose that the claim language be construed to require
that “substantially all” of the 5-ASA be released. First, Plaintiffs draw the Court’s
attention to a part of the specification where the patentees described the claimed
formulation as differing from the prior art in that “there is substantially no leaching
out of the 5-ASA downstream of the colon in the normal patient.” Plaintiffs’ Opening
Br. at 15 (quoting ‘170 patent col. 4 at 3-4). Based on this specification language,
Plaintiffs reason that a skilled artisan would understand this to mean that the
claimed formulation need not achieve perfect release to the right colon and instead
may release an insubstantial amount of drug elsewhere.
Id. at 15-16.
Thus,
Defendants’ construction to impose the standard of perfection on the release,
according to Plaintiffs, departs from the understanding of a skilled artisan. Id.
Plaintiffs further note that their construction is supported by extrinsic evidence.
Plaintiffs’ expert explained that “a skilled artisan would understand that when a
29
drug is formulated, variation in content, manufacturing, and performance will often
lead to less than 100% of the labeled strength being released.” Plaintiffs’ Opening Br.
at 15 (quoting Bodmeier Decl. at 35). As such, release from a dosage form is typically
considered complete when “a substantial amount of drug (generally around 80%)” is
released. Id. Indeed, the official specifications for drug products listed in the United
States Pharmacopeia (“USP”) in 1980 indicate that “release” is considered complete
when a substantial amount (i.e., approximately three-quarters of the drug product)
is released from the dosage form. Id. at 16 (quoting Bodmeier Decl. at 37-40).
Plaintiffs additionally note that, as set forth in the description of the dissolution test
specifications in the General Chapter of the 1980 USP, it was not expected that each
and every tablet meet that specification. Rather, the USP anticipates that, on
average, 75% to 80% of the drug will be released in the intended location. Id. (citing
Bodmeier Decl. at 39).
Regarding the amount of the drug to be released, the Court finds that the
phrase “substantially all” represents what the patentees intended to claim. Although
the term “all” was not included in the patent itself, the Court recognizes that the
patentees have repeatedly used that term during prosecution of the patent. However,
in the Court’s view, they did not intend the term “all” to mean 100%. To release 100%
of 5-ASA to the right side of the colon would be impractical, if not impossible.
Furthermore, the ordinary and customary meaning of the term in the pharmaceutical
industry was, as Plaintiffs point out, the average of 80%—not 100%. Because the
30
term “substantially all” properly represents this consensus, the Court agrees with
Plaintiffs regarding this issue.
The Court also finds, however, that the term “reliable” properly illustrates the
manner in which the release of the drug was intended to occur. As Defendants
correctly indicate, the term “reliable” was repeatedly used throughout the prosecution
history and the specification. More importantly, it is the term “reliable” that the
patentees used in pointing out the prior art’s disadvantage, as well as in presenting
their invention to the Patent Office, and thus to the world. See e.g., ‘170 patent, col.
3 at 61-66. Moreover, given that such a term implies consistency in performance, the
Court agrees with Defendants that the proper construction would include the
meaning of the term “reliable.”
Accordingly, I construe the pertinent language of claims 1, 6, and 7 as follows:
Whereby substantially all of the 5-ASA reliably leaves the
dosage form in the ascending colon and no amount of the 5ASA is released prior to the dosage form reaching the distal
ileum.
By including the qualifiers substantially and reliably, this construction reflects that
the drug will almost always be released in the colon yet the construction leaves room
for the possibility that it might occasionally begin release in the distal ileum. By
stating that no amount is released prior to the dosage form reaching the distal ileum,
the construction makes clear that the drug may not be released upstream. As the
patentees emphasized throughout the specification and prosecution history, pre-distal
ileum release was replete in the prior art.
31
In my view, this is how a person of ordinary skill in the art would understand
the above claim terms and, while avoiding the error of importing a limitation from the
specification into the claim language, this construction avoids the converse evil of
divorcing the claim language from the specification. This construction “capture[s] the
scope of the actual invention more accurately,” Phillips, 441 F.3d at 1324, than both
parties’ proposed constructions which reflect the all-or-nothing approach of fully
embracing or rejecting dissolution and release in the distal ileum. I, further, find it
unnecessary to consider the testimony of the parties’ dueling experts who each offer
opinions in support of their client’s constructions. Because the intrinsic evidence
makes the patentee’s intention clear, resort to extrinsic evidence is not required but
left to the Court’s discretion. See Atofina v. Great Lakes Chemical Corp., 441 F.3d
991, 996 (Fed. Cir. 2006); Phillips, 441 F.3d at 1312-17. I see no need to resort to
expert testimony here.
B.
“Insoluble in gastric juice”
Claim language in claim 1 of the ‘170 patent (and, by default, the dependent
claim 6) indicates that the coating used in the patentees’ carrier system consists of
“a layer which is insoluble in gastric juice and in intestinal juice below pH 7 but
soluble in colonic intestinal juice.” The parties’ claim construction dispute revolves
around both the meaning of “layer” and the meaning of “insoluble,” although their
arguments relating to these two terms are intertwined. They proposed the following
claim constructions.
32
Claim Language
Plaintiffs’ Construction
Defendants’ Construction
A layer which is insoluble in
gastric juice and in intestinal
juice below pH 7 but soluble
in colonic intestinal juice
(Claim 1)
The dosage form is coated with
at least one layer that has
sufficient thickness so that the
coating does not fully dissolve
or disintegrate in gastric juice
and in intestinal juice below pH
7, but does dissolve or
disintegrate in colonic intestinal
juice.
None of the layer dissolves
(i.e., the layer is insoluble) in
aqueous medium below pH 7
but the layer does dissolve
below pH 7.5. This excludes
layers containing mixtures of
Eudragit S and Eudragit L.
Defendants contend that the term “insoluble” in claim 1 should be interpreted
according to its ordinary and customary meaning to a person of ordinary skill in the
art at the time of the invention. In support of their position, Defendants cite
technical treatises in the 1980 time frame, including Pharmaceutical Sciences,
wherein the term “insoluble” was defined in descriptive terms to mean no more than
one part of solute dissolves in 10,000 parts of solvent. See e.g., Koh Decl., Ex. B at
PAR24480. In Defendants’ view, an insoluble layer will have no more than 0.01% of
the layer dissolve in gastric or intestinal juices below pH 7.
Defendants further rely on language in the specification where, in describing
the characteristics of copolymers used in the prior art, the patentees explained the
difference between two copolymers as follows:
Such a copolymer (available under the Registered Trade
Mark “Eudragit” S) … is known to be insoluble in gastric
juice and poorly soluble in intestinal juice while an
analogous copolymer (available under the Registered Trade
Mark “Eudragit” L) … is insoluble in gastric juice but is
readily soluble in intestinal juice.
33
‘170 patent col. 2 at 31-40. Based on this language, Defendants argue that the
patentees understood that the term “insoluble,” in accordance with its ordinary
meaning, is the same as or less soluble than “poorly soluble,” and differs in scale from
“readily soluble.” Defendants’ Open. Br. at 8.
Defendants also emphasize the prosecution history where the patentees
distinguished their claimed dosage form from other dosage forms with a coating layer
containing a mixture of Eudragit S and Eudragit L in a 1984 amendment. There, the
patentees explained that such a coating layer “does not in fact achieve the desired
result” because such coatings would “commence disintegration” and “commence
dissolution” below pH 7, whereas their claimed dosage form showed “no
disintegration” below pH 7 (such as at pH 6.7 or 6.8). File History, 06/482,331 App.,
Sept. 26, 1984 Amendment at 8-9 (Koh Decl., Ex. F at WC372-73). According to
Defendants, this prosecution history confirms that the patentees intended for the ‘170
patent to cover only those coatings where none of the layer dissolved below pH 7, i.e.,
those that did not commence disintegration and remained fully intact while in pH 7
fluids. Finally, Defendants rely on an in vitro study (“In Vitro Study”) disclosed by
the patentees in the prosecution history that could be read to suggest that mixtures
of Eudragit S and L mixtures are disavowed.7
7
“In vitro’ experiments are performed in artificial environments outside
living organisms (such as in a test tube or culture media), while ‘in vivo’ experiments
are performed within living organisms.” In re ‘318 Patent Infringement Litig., 583 F.3d
1317, 1325 (Fed. Cir. 2009).
34
By contrast, Plaintiffs argue that the claim language is easily understood by a
skilled artisan and requires no further construction. However, should the Court
determine that the language requires construction, Plaintiffs suggest that it should
be construed to mean that “the dosage form is coated with at least one layer that has
sufficient thickness so that the coating does not fully dissolve or disintegrate in
gastric juice and in intestinal juice below pH 7, but does dissolve or disintegrate in
colonic juice.” Plaintiffs’ Opening Br. at 17. In support of their position, Plaintiffs
rely on the testimonies of both parties’ experts, wherein they explain that the
solubility of a coating layer must be evaluated based on the performance of the layer
as a whole, not individual components. TR at 47:3-48:21; Bodmeier Decl. at 48.
Because the performance of the layer will depend upon the “chemical and physical
interaction” of all of the components rather than each component standing alone,
Plaintiffs claim that the phrase “[n]one of the layer” in Defendants’ construction is
at odds with the claim language, which refers to the coating “layer” as an indivisible
construct. Plaintiffs’ Opening Br. at 17-18.
Plaintiffs also note that because the claim language refers to biological fluids,
Defendants’ construction, which is based upon in vitro performance rather than in
vivo, should be given less weight in claim construction. Id. at 18. In addition,
Plaintiffs point out that Defendants’ construction was adopted from extrinsic
evidence (in this case, technical treatises). Id. Because Plaintiffs believe that the
intrinsic evidence clearly showed performance of the coating is to be judged on a
functional basis, not based on an in vitro dissolution test, they argue that the Court
35
should not rely on Defendants' construction. Id. (citing Phillips, 415 F.3d at 1319)
(extrinsic evidence is unlikely to result in a reliable interpretation of patent claim
scope unless considered in the context of the intrinsic evidence).
As an initial matter, the Court find its helpful to first separate out the
arguments relating to the definition of the “layer.” I conclude that the solubility of
the layer is to be evaluated as a whole, rather than by individual components. The
claim itself refers to “a layer, which is insoluble in gastric juice ....” The plain
language of the claim makes clear that only one layer is anticipated hence further
resort to intrinsic or extrinsic evidence is not required to construe the term.
There is one clarification required, however. At oral argument, the Court
inquired whether the solubility requirement is concerned with the performance of the
entire layer or whether it is focused on those elements of the layer that would prevent
release of the active ingredient (the 5-ASA) to the colon. TR at 49-52. Plaintiffs
agreed that the impetus underlying the claim language is to ensure that the
mesalamine is released at the appropriate location in the body.
In my view, it is critical for the claim construction to take into account this
clarification which gives meaning to the “release . . . to the right side of the colon”
claim language. Claim 1 claims
a layer which is insoluble in gastric juice and in intestinal
juice below pH 7 but soluble in colonic intestinal juice,
whereby the dosage form releases the 5-amino-salicylic-acid,
salt or ester to the right side of the colon.
36
‘170 patent, col. 10:18-20 (emphasis added). By using “whereby” the patentees made
clear that the layer is designed to ensure release of the 5-ASA specifically to the right
side of the colon and not before reaching the distal ileum. Hence the layer solubility
requirement must be understood in this context. See Bicon, Inc. v. Straumann Co.,
441 F.3d 945, 950 (Fed. Cir. 2006) (“[C]laims are interpreted with an eye toward
giving effect to all terms in the claim.”).
In terms of the definition of insolubility, even Defendants agreed at oral
argument that the coating may dissolve in some small amount and still be considered
“insoluble.” See TR at 70-71. The parties disagree, however, as to what amount of
disintegration is permissible under the claim language. In light of this disagreement,
the Court finds that “insoluble” must be construed. Moreover, as explained in more
detail herein, the Court finds that the patentees did not act as their own
lexicographer and create a special definition of “insoluble” in the patent; neither the
claim, the specification, nor the prosecution history specify how the term should be
defined. Accordingly, the Court must determine the ordinary and customary meaning
of the term.
Plaintiffs’ proposed construction of insoluble, which appears below, is
overbroad.
The dosage form is coated with at
least one layer that has sufficient
thickness so that the coating does
not fully dissolve or disintegrate
in gastric juice and in intestinal
juice below pH 7, but does
dissolve or disintegrate in colonic
intestinal juice.
37
Under this construction, practically any layer would be considered “insoluble” as long
as at least some components of the layer remain intact below pH 7. For example, as
Defendants pointed out in their opening brief, even if 95% of a coating layer dissolves,
such a layer would be considered “insoluble” under Plaintiffs’ proposed construction
because it had not “fully” dissolved or disintegrated. And, as Plaintiffs noted at oral
argument, the coating is typically comprised of additional agents, such as coloring
agents. TR at 47-48. Under Plaintiffs’ “fully” dissolved construction, the coating
could be deemed insoluble when only the coloring agent has not dissolved. Without
any objective standard to define “fully,” this Court is not convinced that Plaintiffs’
construction reflects the ordinary and customary meaning of “insoluble.”
In addition, by stating that the “layer . . . has sufficient thickness so that the
coating does not fully dissolve ....,” Plaintiffs’ construction suggests that the thickness
of the coating determines the polymer’s solubility. This is problematic because the
specification treats solubility and thickness as distinct elements of the coating that,
when properly combined, each helps ensure that the drug is “dumped” into the colon
for topical treatment.
The specification describes the invention as “[a] solid oral dosage form . . .
coated with an anionic polymer, which is insoluble in gastric juice and in intestinal
juice below pH 7 but soluble in colonic intestinal juice, in a sufficient amount that the
oral dosage form remains intact until it reaches the colon.” ‘170 patent, Abstract
(emphasis added). See also id. at 4:26-31 (same). By describing the polymer as
“insoluble in gastric juice,” the patentees made clear that solubility relates to the type
38
of anionic polymer that must be employed. Only after describing the type of polymer
to be employed, i.e., one that is insoluble in gastric juice, do the patentees note that
the dosage form must be coated with a “sufficient amount” of that polymer. Hence
the “sufficient amount” language addresses how much of the polymer must be used
in order to facilitate delivery of the drug to the colon.
Furthermore, the patentees distinguish the invention from the prior art by
explaining that the invention “coat[s] a solid oral dosage form with a sufficient
thickness of a partly methyl esterified methyacrylic acid polymer which does not
dissolve in aqueous medium below pH 7 but does dissolve below pH 7.5,” and that
this type of coating is “entirely new in concept” because it ensures that “dissolution
or disintegration does not occur until entry of the coated dosage form into the colon.”
Id. at 3:63 - 4:11 (emphasis added). Here, too, the patentees describe the type of
polymer in terms of its solubility and separately note that the polymer must be
employed in a certain thickness. Therefore, Plaintiffs’ proposed construction, which
focuses only on the thickness of the coating, as opposed to both the thickenss and the
solubility of the polymer, is inconsistent with the specification.8
8
This reading of the specification is supported by the deposition testimony
of Defendants’ expert, Dr. Elder, who explains that “[a] coating does not become
insoluble by making it larger or thicker; rather, solubility is an intrinsic chemical
property which does not change with thickness.” Elder Decl., ¶ 12. Moreover, while
Plaintiffs rely on the file history statement, made in prosecution of the ancestor ’386
patent application, that “[t]he requirement of coating thickness is functional, in the
sense that it must be thick enough to keep the tablet substantially intact until the
colon is reached but not so thick as to permit the tablet to be excreted ....” File History,
07/584,386 App., June 4, 1991 Amendment at 10 (Ainsworth Decl., Exh. M at WC532),
that statement merely emphasizes that thickness can affect whether the drug is
39
Although Defendants’ proposed construction does not suffer from the same
infirmities as does Plaintiffs, Defendants’ construction is problematic for a different
reason. As noted, Defendants propose the construction that “none of the layer
dissolves ....”9 However, they conceded at oral argument that an insubstantial
amount may dissolve. In light of this concession alone, Defendants’ “none of the
layer” construction must be rejected.
More to the point, neither party has pointed to any express definition of
“insoluble” that is clearly set forth in the specification or the prosecution history, thus
I conclude that the patentees did not act as their own lexicographer. Accord Aventis
Pharma S.A. v. Hospira, Inc., 675 F.3d 1324, 1331-32 (Fed. Cir. 2012) (concluding
that “patentee did not narrow the ordinary meaning of ‘perfusion’ . . . by either acting
as its own lexicographer or disclaiming claim scope” where nothing in specification
or prosecution history clearly addressed definition of that term). Where a patentee
does not clearly “assign to a term a unique definition that is different from its
ordinary and customary meaning,” by acting as its own lexicographer, the ordinary
and customary meaning of that term applies. Laryngeal Mask Co. Ltd. v. Ambu, 618
F.3d 1367, 1372 (Fed. Cir. 2010).
released in the desired location in the digestive tract. It does not speak to the
solubility of the polymer used in the coating.
9
Defendants further seek to include in their construction a limitation
excluding mixtures of Eudragit S and Eudragit L. For the reasons explained infra, I
reject that limitation as unsupported by the specification and prosecution history.
40
Accordingly, I turn to dictionary definitions of “insoluble” to aid me in
discerning the ordinary and customary meaning of that term. See Zircon Corp, v.
Stanley Black & Decker,Inc., 452 Fed.Appx. 966 (Fed Cir. 2011) (considering
dictionary definition where claim language is broad enough to encompass more than
one meaning). “In some cases, the ordinary meaning of claim language as understood
by a person of skill in the art may be readily apparent even to lay judges, and claim
construction in such cases involves little more than the application of the widely
accepted meaning of commonly understood words. In such circumstances, general
purpose dictionaries may be helpful.” Phillips, 415 F.3d at 1314. Moreover, resort
to scientific and technical dictionaries is appropriate where the intrinsic evidence
does not define a scientific term to be construed. See Atofina v. Great Lakes
Chemical Corp., 441 F.3d 991, 996 (Fed. Cir. 2006).10 I find this circumstance to be
an appropriate one for resort to a scientific dictionary definition, and turn to the
definition of “insoluble” in the 1980 Pharmaceutical Sciences excerpt in the record.
The 1980 Pharmaceutical Sciences excerpt defines “insoluble” as a layer that
will have no more than 0.01% of the layer dissolve. The excerpt explains that “[w]hen
in pharmacopeial texts it has not been possible, or in some instances, desirable, to
10
See also Phillips, 415 at 1318 (“Because dictionaries, and especially
technical dictionaries, endeavor to collect the accepted meanings of terms used in
various fields of science and technology, those resources have been properly recognized
as among the many tools that can assist the court in determining the meaning of
particular terminology to those of skill in the art of the invention. Such evidence, we
have held, may be considered if the court deems it helpful in determining ‘the true
meaning of language used in the patent claims.’”).
41
indicate exact solubility, a descriptive term has been used. The following table
indicates the meaning of such terms:
Descriptive
terms
Parts of solvent
for 1 part of solute
Very soluble
Less than 1
Freely soluble
From 1 to 10
Soluble
From 10 to 30
Sparingly soluble
From 30 to 100
Slightly soluble
From 100 to 1000
Very slightly soluble
From 1000 to 10,000
Practically insoluble, or insoluble
More than 10,000
Koh Decl., Exh. B at PAR24480 (emphasis added). See also Koh Decl., Exh. C at
PAR24560 (same); id., Exh. D (British Pharmacopˆia) at PAR24467 (same).
I conclude that this definition reflects the ordinary and customary definition of
“insoluble” at the time of the initial application that ultimately led to the issuance of
the ‘170 patent. I find it particularly appropriate to rely on this definition here where
the definition does not contradict the intrinsic evidence of record. Compare Advanced
Fiber, 674 F.3d at 1374 (“[W]e conclude that the district court erroneously construed
‘perforated’ using extrinsic evidence that contradicts the intrinsic evidence of
record.”). This definition is consistent with the definition of insoluble from the
McGraw-Hill Dictionary of Scientific and Technical Terms, a scientific dictionary
relied upon by the Federal Circuit in ascertaining the ordinary and customary
42
meaning of claim terms. See e.g.,Wavetronix LLC v. EIS Electronic Integrated Sys.,
573 F.3d 1343, 1333 (Fed. Cir. 2009) (relying on The McGraw-Hill Dictionary of
Scientific and Technical Terms 1159-60 (5th ed. 1994) for its definition of “local
device”); L.B. Plastics, Inc. v. Amerimax Home Prods., Inc., 499 F.3d 1303, 1308 (Fed.
Cir. 2007) (affirming district court’s reliance on The McGraw-Hill Dictionary of
Scientific and Technical Terms 2288 (6th ed. 2002) for its definition of “welding”);
Atofina, 441 F.3d at 999 (citing The McGraw-Hill Dictionary of Scientific and
Technical Terms 307 (4th ed. 1989) for its definition of “catalyst”). The McGraw- Hill
definition of insoluble is “[i]ncapable of being dissolved in another material ....” The
McGraw-Hill Dictionary of Scientific and Technical Terms 1084 (6th ed. 2002). Like
the USP treatise definition, the McGraw-Hill definition makes clear that only a
minute amount of the layer may dissolve.11
As noted earlier, Plaintiffs additionally argue that reliance on this definition is
inappropriate because it reflects an in vitro dissolution standard while, in Plaintiffs’
view, the specification and claims make clear that solubility is to be determined on
functionally, i.e., in vivo, based on how it performs in actual gastrointestinal fluids.
I reject this argument. For one, the specification refers to “aqueous medium” to
describe the solubility of prior art uses of Eudragit S and Eudragit L. See ‘170
patent, col. 2:45-47. Furthermore, Plaintiffs relied on both in vivo and in vitro studies
11
Moreover, while Plaintiffs urge the Court not to consult the USP treatise
in defining “insoluble,” Plaintiffs rely on this same treatise in support of their
“substantially all” proposed construction language discussed supra.
43
throughout the prosecution history and, indeed, acknowledge that “in vivo
performance may be predicted through in vitro tests ....” Pl. Open. Br. at 18 n.10
(emphasis in original). While Plaintiffs suggest that this reliance does not justify
incorporating an in vitro standard into the claim construction, there is likewise no
basis for reading into the claim an in vivo-based dissolution standard. Hence, I find
reliance on the Pharmaceutical Sciences definition appropriate here.
Thus, giving the terms “layer” and “insoluble” meaning in the context of claims
1 and 6, I construe “a layer which is insoluble in gastric juice and in intestinal juice
below pH 7 but soluble in colonic intestinal juice” to mean:
a layer of which no more than 0.01% of that layer dissolves
in gastric or intestinal juices below pH 7, but does dissolve
or disintegrate in colonic intestinal juice.
This construction differs from Defendants’ construction in that it does not require
that “none” of the layer dissolve. It allows for .01% of the layer to dissolve or
disintegrate. It also differs from Plaintiffs’ construction in that it is more definite
than “fully” dissolve. In the Court’s view, this construction best harmonizes the claim
language, the specification, and the prosecution history.
C.
Eudragit S and L Limitation (Claims 1 and 7)
Defendants contend that the patentees clearly and unmistakably excluded
layers of mixtures of Eudragit L and Eudragit S from the claimed invention, both in
the specification and during prosecution. Turning first to the specification language,
Defendants argue that the patentees distinguished prior art formulations having
coating layers of Eudragit L alone, as well as mixtures of Eudragit L and Eudragit
44
S, because in all cases such coatings dissolved below pH 7. ‘170 patent, col. 3 at
46-49; see also id., col. 2 at 49-50 (“As far as we are aware, said mixtures [of Eudragit
S and Eudragit L] invariably dissolve below pH 7.”). By contrast, the patentees
emphasized that their invention does not dissolve in such conditions. ‘170 patent, col.
3 at 61-66.
Second, according to Defendants, the prosecution history clearly disclaims the
mixtures of Eudragit L and Eudragit S from claim 1. In an amendment filed on May
20, 1985, during the prosecution of an ancestor patent application (the ’727
application), the patentees stated that they amended the claims “to make them more
specific to the polymer used in the working examples, Eudragit S.” File History,
06/482,331 App., May 20, 1985 Preliminary Amendment at 6 (Koh Decl., Exh. I at
WC391).
In their explanation, the patentees stated “the purpose of this
characterization is to make clear that mixtures of Eudragit L and Eudragit S are
excluded from the claims.” Id. at 7 (Koh Decl., Exh. I at WC392) (emphasis in
original). Defendants further argue that the patentees reiterated in several of the
early ancestor applications that coating layers containing mixtures of Eudragit L and
Eudragit S were known in the prior art, and would not achieve the desired claimed
result—releasing the 5-aminosalicylic acid to the right side of the colon:
•
“Applicants’ own experience has revealed that mixing
of Eudragit S and Eudragit L does not, in fact,
achieve the desired result … capsules thus coated
would probably commence disintegration on entering
the duodenum which is a pH of 6.8 and will not
remain intact until reaching the colon.” See File
45
History, 06/482,331 App., Sept. 26, 1984 Amendment
at 9 (Koh Decl., Ex. F at WC372-373).
•
“With combinations of Eudragit L and Eudragit S,
applications were still unable to achieve the desired
result of capsules which reliably broke in the very
distal ileum or caecum.” Id. at 11 (Koh Decl., Ex. F at
WC374).
•
“Mixtures of [Eudragit] L + S polymers would not be
suitable.” File History, 06/482,331 App., In Vitro
Study at 4 (Koh Decl., Ex. H at WC421) (“In Vitro
Study”).
•
For Eudragit L and Eudragit S coating mixtures, “in
all cases the coating dissolved below pH 7.” File
History, 06/482,331 App., Oct. 14, 1983 Amendment
at 8 (Koh Decl., Ex. J at WC346) (emphasis in
original).
•
“A film of Eudragit L and Eudragit S in the ration 1:2
commences dissolution at about pH 6.7.” File
History, European Patent, Dec. 1, 1988 Declaration
at ¶ 2 (Koh Decl., Ex. G at EX461, 2).
In addition, Defendants note that the patentees even submitted to the Patent
Office data, i.e., the In Vitro Study, with coatings containing mixtures of Eudragit L
and Eudragit S. In the study, the patentees demonstrated that in an aqueous
solution buffered to a pH 6.8, either “[c]omplete disintegration” occurred or
“[f]ragments remained,” whereas there was “[n]o disintegration” for the coating only
containing Eudragit S. In Vitro Study at 1-4. As such, Defendants believe that this
is further evidence that the patentees did not believe mixtures of Eudragit L and
Eudragit S would be suitable for the claimed invention. Id. at 4.
46
As extrinsic evidence, Defendants further indicate that Brian Evans, one of the
inventors, stated during his deposition on September 17, 2009, that when even a
small amount of Eudragit L was added to the coating layer, the Eudragit L would
cause the coating to “dissolve slightly” below pH 7 and therefore would not be a
workable formulation:
Question: Do I take it from these initial dissolution results
you ruled out any amount of Eudragit L in the formula?
Answer: Yes … it was unsuitable because we wanted the
product to remain intact until the distal ileum, so after
looking at it in an in vitro situation we decided to - not to go
ahead with it.
Question: The presence of a small amount of Eudragit L
would have caused the coating to dissolve slightly below pH
7. Is that accurate?
Answers: Yes. What Rohm Pharma [the manufacturer of
the Eudragit products] give in their literature are the
various ratios you could use, and the pH ranges that they
would then disintegrate in, so I took that as a guide, but did
a whole range of them, so it was too early. Whatever
concentration we used with the [Eudragit] L, it was going to
go too early for us.
Koh Ex. E at 187:12-188:16.
Based on this testimony, Defendants argue that
extrinsic evidence also clearly supports their position that the patentees disclaimed
mixtures of Eudragit L and Eudragit S from claim 1.12
12
The Court notes, at the outset, that it will not base its construction of the
claims on an inventor’s subjective intent. See Howmedica Osteonics Corp. v. Wright
Medical Technology, Inc., 540 F.3d 1337, 1346-47 (Fed. Cir. 2008) (“[t]he subjective
intent of the inventor when he used a particular term is of little or no probative weight
in determining the scope of a claim.”)
47
Plaintiffs contend that Defendants’ proposed construction is unsupported by the
claim language, and should be rejected. For one, Plaintiffs argue, Defendants’
reliance on prosecution history statements wherein the inventors found mixtures of
Eudragit L and Eudragit S not suited for their purposes is misplaced. In the In Vitro
Study, the patentees conducted a series of experiments to find the optimal coating
composition for 5-ASA, using three different types of formulas. Plaintiffs especially
point out that the inventors used only Formula 3, which Plaintiffs contend was
comprised of a mixture of Eudragit S and Eudragit L,13 in transit time studies as well
as coating thickness studies. TR at 23:4-26:4. Based on these test reports, Plaintiffs
argue that the patentees intended to claim mixtures of Eudragit L and Eudragit S.
Id. Although Plaintiffs acknowledge that the report contained the statement that
“[m]ixtures of L+S polymers would not be suitable,” they contend that, when read in
context, this statement does not give rise to the level of an express disclaimer
sufficient to limit the scope of the claim.
As to the alleged disclaimer made during prosecution of the ’331 application,
Plaintiffs concede that the patentees amended the proposed claims early in 1985 to
exclude the mixture of Eudragit L and Eudragit S. However, Plaintiffs contend that
the purpose of the amendment was to limit the scope of that particular ancestor
application (the ’331 application). More to the point, Plaintiffs argue, the amended
language in the ’331 application was ultimately adopted to the ‘171 patent—not the
13
57.
More details of the composition of Formula 3 are discussed infra at ¶ 5648
‘170 patent. Hence Plaintiffs reason that such disclaimer is only valid as to the ‘171
patent and that such limitation should not be read into claims of the ‘170 patent.
Plaintiffs apply this same rationale to a similar disclaimer found in the prosecution
history of the ’727 application.
Plaintiffs further point to a responsive amendment made in 1995 in support of
their proposed claim construction. In this amendment, the patentees explained that
the reason they submitted the divisional application (which resulted in the issuance
of the ‘170 patent) was to provide for other coatings to be used. See File History,
06/401,696 App., Nov. 17, 1995 Responsive Amendment at 4-5 (Ainsworth Decl., Exh.
E at WC132-33). Moreover, there are several parts of the ’170 specification wherein
the patentees indicate that other polymers are also acceptable:
•
“It is expected that any anionic polymer having the
dissolution profile specified above can be used in the
practice of the invention subject, of course, to
compatibility with the relevant active agent.” ‘170
patent, col. 4:35-38 (emphasis added).
•
“Obviously, a certain amount of trial-and-error
experimentation will be required before ascertaining
the optimum thickness of a particular polymer on a
particular solid oral dosage form but such
experimentation is well within the capability of a
man of average skill in the art.” Id., col. 4:67-5:5
(emphasis added).
49
Because the ‘170 patent refers to non-Eudragit S polymers, Plaintiffs argue that the
disclaimer of the mixture of Eudragit L and Eudragit S is not applicable to the claims
of the ‘170 patent.14
While Defendants’ arguments seem persuasive at first blush, it becomes clear
upon reading the prosecution history as a whole that the prosecution history
statements relied upon by Defendants are from ancestor applications that must be
construed as applicable only to the related ‘171 patent which expressly excludes
mixtures of Eudragit L and Eudragit S. Thus, while Defendants point to language
in the prosecution history of the ancestral ’727 application stating that “mixtures of
Eudragit L and Eudragit S are excluded from the claims,” ’727 App., May 20, 1985
Preliminary Amendment, at 1-4 (Ainsworth Decl., Ex. N) (emphasis in original),15 in
the subsequent Divisional Application that resulted in the ‘170 patent, the patentees
indicated that they were seeking broader claims than previously sought in such
ancestral applications.
14
Plaintiffs further argue that, because they interpret the solubility
limitation in claim 1 as relevant only to its performance in the body, i.e., in vivo
performance, that Defendants’ construction to exclude the mixture of Eudragit L and
Eudragit S is erroneous. I do not address this argument because I conclude, for the
reasons explained herein, that the patentees did not disclaim mixtures of Eudragit L
and Eudragit S.
15
See id. at 6 (“The Examiner lists a series of some six different expressions
that are considered unjustified by the disclosure of the specification. In response to
this objection, applicants have amended their claims to make them more specific to the
polymer used in the working examples, Eudragit S.”)
50
In this connection, Plaintiffs argue that the reason the patentees divided the
then-pending ’167 continuation application into what was ultimately issued as two
separate patents was to patent the Eudragit S coating formulation through the ‘171
patent yet patent multiple coating formulations through the ‘170 patent. To support
this argument, they point to a responsive amendment to the Divisional Application
which states that the claims are “broad.” File History, 06/401,696 App., Nov. 17, 1995
Responsive Amendment at 4 (Ainsworth Decl., Exh. E at WC132).
The Court does not find use of the word “broad” alone makes clear the
patentees’ intent to encompass other anoinic formulations such as a mixture of
Eudragit S and Eudragit L, however, additional language in the responsive
amendment supports the view that such mixtures were not excluded. The text
explains that, while one of the examples in the specification teaches Eudragit S,
[i]t is submitted that given the task of providing other
coatings insoluble in gastric juice and intestinal juice having
a pH below 7 but soluble in colonic intestinal juice that
would release 5-ASA from the dosage form to the right side
of the colon, one skilled in the art of drug composition
formulation and pharmacokinetics could do so without
undue experimentation.
Id. (emphasis added). Had the patentees intended to limit the scope of the ’170
patent to Eudragit S coatings, there would have been no need to discuss how “other
coatings” could be formulated.
Importantly, the prosecution history further suggests that the patentees
envisioned the use of not just “other coatings” but other polymers containing mixtures
of anionic groups. In an amendment to the 08/032,167 ancestor patent application,
51
the patentees distinguished the use of Eudragit coatings in the prior art by stating
that “[t]here is no suggestion [in the art] that any tablet should be coated with
Eudragit S coatings of the thickness (60 to 150 microns) required by the present
Invention. Further, there is no reference to the use of any Eudragit coating to
maintain tablets or other oral dosage forms substantially intact until the colon is
reached.” File History, 08/032,167 App., April 18, 1994 Amendment at 16 (Koh Decl.,
Exh. N at WC621). By contrasting “Eudragit S” and “any Eudragit coating,” the
patentees made clear that they intended to claim additional Eudragit coatings or
mixtures thereof. Moreover, since the patentees subsequently limited the ‘171 patent
to only Eudragit S coatings, their reference in the prosecution history to “any
Eudragit coating” should be interpreted in the context of ‘170 patent to potentially
include mixtures of Eudragit S and Eudragit L.
More importantly, the specification for the ‘170 patent explains that Eudragit
S and Eudragit L are both anionic copolymers. ‘170 patent, col. 2:33-35. For
Eudragit S, the ratio of free carboxyl groups to ester groups is approximately 1:2. For
Eudragit L, in contrast, the ratio is 1:1. Consistent with this description of Eudragit
S’s ratio of free carboxyl groups to ester groups, the ‘171 patent claims include the
express limitation that “said oral dosage form is coated with a . . . layer of an anionic
copolymer of methacrylic acid and methacrylic acid methyl ester in which the ratio
of free carboxyl groups to ester groups is about 1:2 ....” ‘171 patent, claims1, 9, and
12 (emphasis added). The ‘170 patent claims, in contrast, do not include an express
Eudragit S coating formulation limitation.
52
For this reason, it is inappropriate to interpret the ’727 ancestor patent file
history statement, which incorporates Eudragit S, as limiting the ‘170 patent. It is
better to view the statement as related to the ‘171 patent claims which explicitly
incorporate the Eudragit S formulation. It is true that “prosecution disclaimer may
arise from disavowals made during the prosecution of ancestor patent applications.”
Ormco Corp. v. Align Technology, Inc., 498 F.3d 1307, 1314 (Fed. Cir. 2007). But, just
as “the prosecution of one claim term in a parent application will not limit different
claim language in a continuation application,” Invitrogen Corp. v. Clontech Labs.,
Inc., 429 F.3d 1052, 1078 (Fed. Cir. 2005), so too will prosecution disclaimers relating
to claim language in an ancestral patent fail to limit different claim language in a
divisional application. See Biogen, 318 F.3d at 1140 (“When the applicant is seeking
different claims in a divisional application, estoppel generally does not arise from the
prosecution of the parent.”)
This is not to say that the prosecution history is a model of clarity. In my view,
the patentees could have more precisely explained the scope of the claims they sought
through the divisional application leading to the ‘170 patent. The Federal Circuit has
noted that this sort of lack of clarity is usually because “the prosecution history
represents an ongoing negotiation between the PTO and the applicant, rather than
the final product of that negotiation ....” Phillips, 415 F.3d at 1317. Nevertheless,
courts are directed to consider the prosecution history as a whole.
Martek
Biosciences Corp. v. Nutrinova, Inc., 579 F.3d 1363, 1377 (Fed. Cir. 2009) (“In
determining whether there has been a clear and unmistakable surrender of subject
53
matter, the prosecution history must be examined as a whole.”) (quoting Bayer AG
v. Elan Pharm. Research Corp., 212 F.3d 1241, 1252 (Fed. Cir. 2000)). Reading the
totality of the prosecution history here, and considering the Divisional Application
language, I conclude that the patentees did not clearly disclaim mixtures of Eudragit
S and Eudragit L for the ‘170 patent.
Review of the specification for the’170 patent further supports my conclusion
that the patentees did not disavow mixtures of Eudragit S and Eudragit L. On the
one hand, as Defendants point out, there is language disparaging mixtures of
Eudragit S and Eudragit L. In discussing prior art, the specification states that “as
far as we are aware, said mixtures [of Eudragit S and Eudragit L] invariably dissolve
below pH 7.” ‘170 patent, col. 2 at 49-50. The specification further states that the
mixtures of Eudragit S and Eudragit L in each of the examples disclosed in the
European Specification prior art “dissolved at below pH 7,” which could be
characteristic of Eudragit mixtures comprised in part of Eudragit L. On the other
hand, the specification language states that “any anionic polymer having the
dissolution profile specified above,” ‘170 patent, col. 4 at 35-36 (emphasis added), i.e.,
a polymer that “does not dissolve in aqueous medium below pH7 but does dissolve
below pH 7.5,” id., col. 3:64-66, may be used in the coating. This statement leaves
open the possibility that mixtures of Eudragit S and Eudragit L could be used should
those mixtures be formulated in a manner that meets the dissolution profile. In the
face of this sort of potentiality, it cannot be said that the patentees clearly disavowed
all mixtures of Eudragit S and Eudragit L .
54
In addition, the specification language takes on a more nuanced meaning when
read in context. While the specification states uncompromisingly that “as far as we
are aware, said mixtures [of Eudragit S and Eudragit L] invariably dissolve below pH
7,” earlier in that same paragraph the patentees explain that the mixtures of
Eudragit S and Eudragit L found in the prior art were “usually employed to provide
a coating of between about 25 and about 40 microns thick ....” Id., col. 2:40-42. It is
clear from this preceding sentence that when the patentees state that “said mixtures
invariably dissolve below pH 7,” they are referring to mixtures employed in coatings
of about 25 to 40 microns thick. As explained supra, the specification further makes
clear that both the thickness of the coating and the type of polymer employed help
ensure that the drug is delivered to the ascending colon. In this light, the patentees’
seemingly absolute statement is not as clear and unmistakable as it first appears.
Moreover, the Federal Circuit has made clear that criticism of a particular
embodiment or technique “d[oes] not rise to the level of clear disavowal.” Thorner,
669 F.3d at 1366 (quoting Epistar Corp. v. Int'l Trade Comm’n, 566 F.3d 1321, 1335
(Fed. Cir. 2009)).16
16
While Defendants cite Astrazeneca AB, Aktiebolaget Hassle, KBI-E, Inc.
v. Mutual Pharmaceutical Co., Inc., 384 F.3d 1333, 1337 (Fed. Cir. 2004), for the
proposition that critique of prior art serves as a disavowal, the Thorner Court limits
Astrazeneca to its facts. Specifically, Thorner describes Astrazeneca as “limiting a
patentee to particular examples of solubilizers when it stated in the specification that
‘[t]he solubilizers suitable according to the invention are defined below.” Thorner, 669
F.3d at 1366 (emphasis in original). Defendants have not pointed to similar language
in the specification here.
55
In concluding that the patentees did not clearly and unmistakably disavow
mixtures of Eudragit S and Eudragit L, I considered the In Vitro Study cited by the
parties but find that an internal ambiguity renders it unhelpful. The study begins
by comparing Eudragit S and L. Koh Decl., Exh. H at 1. It then sets out three
formulas: Formula 1—Eudragit S only; Formula 2—a 1:2 ratio of Eudragit L to S;
and Formula 3—another 1:2 ratio of Eudragit L to S. Id. at WC418-419. At the
conclusion of the in vitro test results, the study states that “Mixtures of L + S
polymers would not be suitable.” and that “a coating of neat Eudragit-S should be
capable of remaining intact ....” Id. at WC421. Thereafter, the study describes an in
vivo “transit time” test involving capsules “coated with an excess of Eudragit-S (200
ml of Eudragit-S Formula 3) ....” Id. The result of this test is that “200 mls of a 3%
Eudragit-S solution . . . was sufficient to protect the capsules from disintegration.”
Id. at WC423. Finally, the study describes a coating thickness, in vitro test designed
to discover “the optimum range of acrylic coating thickness which would allow
successful delivery of the dosage form to the terminal ileum/ascending colon and then
to dissolve in the environmental pH thereby enabling the capsule or tablet to rapidly
disintegrate.” Id. The study does not state what sort of coating—Eudragit S alone
(i.e., neat Eudragit S) or a mixture of Eudragit S and Eudragit L—was used.
Both the Court and the parties considered competing interpretations of the
study at length during oral argument. See TR at 24-25, 61, 93-94, 106-111. Most of
the confusion stems from the study’s use of what appears to be two different Formula
3s. In the initial in vitro test, the authors refer to Formula 3 as a 1:2 ratio of
56
Eudragit L (1 g) to Eudragit S (2 g). Yet, in the in vivo transit time test results, the
authors refer to Formula 3 as 200 ml of Eudragit S. Despite this ambiguity, Plaintiffs
seek to rely on the results of the coating thickness test to provide context for the
statement in the initial in vitro test that “[m]ixtures of L + S polymers would not be
suitable.” Conversely, Defendants rely on the aforesaid statement as a clear and
unmistakable disavowal. In my view, with the inherent ambiguity in the study, I
cannot fully discern the import and context of the “[m]ixtures . . . ” statement and,
consequently, do not find that it supports Defendants’ argument.
In reaching my conclusion that mixtures of Eudragit S and Eudragit L are not
excluded from the ‘170 patent, I further note the Federal Circuit’s acknowledgment
of the inherent difficulty in construing claims where predecessor applications or
patents were drawn to narrow claims, yet claims in the successive applications are
arguably broader than the invention described in the specification. See Saunders
Group, Inc. v. Comfortrac, Inc., 492 F.3d 1326, 1335-36 (Fed. Cir. 2007). In addition
to posing “interdependent problems of both claim construction and validity,” id. at
1336, the circuit has explained that
the problem is a difficult one, made more so by the failure of
applicants to state expressly to the examiner, whether for
tactical reasons or otherwise, the extent to which they
intended their new claims to depart from the scope of the
claims in the predecessor applications. In many such cases,
as in this one, we and the district court are required to draw
sometimes conflicting inferences from different sources of
guidance as to proper claim construction and to weigh those
conflicting inferences in reaching a conclusion as to the
proper construction.
57
Id.
Perhaps this has been the circumstance here. While I am convinced after a
thorough review of the entire prosecution history and specification that the patentees
did not intend to exclude mixtures of Eudragit S and Eudragit L in the ‘170 patent,
there are certainly aspects of the prosecution history, particularly when read in
isolation, that could lead one to conclude that the mixtures were excluded. Indeed,
some portions of the specification also support that view. Nonetheless, “[p]rosecution
disclaimer does not apply to an ambiguous disavowal.” Computer Docking, 519 F.3d
at 1376. Hence, while the patentees could have certainly better clarified the breadth
of the ‘170 patent claims, I conclude that they did not intend to narrow the claims in
the manner Defendants suggests.
In short, reading the claim language, the
specification, and the prosecution history in conjunction, I find that there is an
insufficient basis for concluding that the patentees clearly disavowed Eudragit S and
Eudragit L mixtures.
D.
pH Limitation for Claim 7
Claim Language
Plaintiffs’ Construction
Defendants’ Construction
said solid oral dosage form
being coated so as to release the
5-amino-salicylic acid, salt or
ester to the right side of the
colon.
Substantially all of the
drug leaves the dosage
form in the distal part of
the small intestine or the
ascending colon.
The coating is insoluble below
pH 7, i.e., Eudragit S, and
thereby reliably releases all of the
active ingredient contained in the
dosage form to the right side of
the colon (i.e., the ascending
colon, and not the terminal
ileum). (emphasis added)
58
Defendants seek to import a pH limitation into claim 7 which, on its face, does
not include such a requirement. This is in contrast to claim 1 which includes that
limitation, as the following comparison illustrates.
Claim 1
1. An orally administrable pharmaceutical composition for
selectively administering 5-amino-salicylic acid, or pharmaceutically
acceptable salt or ester thereof, to the large intestine, comprising a solid
oral dosage form containing a pharmaceutically effective amount for the
treatment of ulcerative colitis or Crohn’s disease of the colon of said 5amino-salicylic acid, salt or ester, said solid oral dosage form being
coated with a layer which is insoluble in gastric juice and in intestinal
juice below pH 7 but soluble in colonic intestinal juice, whereby the
dosage form releases the 5-amino-salicylic-acid, salt or ester to the right
side of the colon.
Claim 7
7. An orally administrable pharmaceutical composition for
selectively administering 5-amino-salicylic acid, or pharmaceutically
acceptable salt or ester thereof, to the large intestine, comprising a solid
oral dosage form containing a pharmaceutically effective amount for the
treatment of ulcerative colitis or Crohn’s disease of the colon of said
5-amino-salicylic acid, salt or ester, said solid oral dosage form being
coated so as to release the 5-amino-salicylic acid, salt or ester to the
right side of the colon.
While comparison of these two claims strongly suggests that the patentees did not
intend for claim 7 to contain a pH limitation, Defendants nonetheless argue that the
limitation should be read into claim 7 from the specification which repeatedly
references the pH solubility requirement and distinguishes prior art on that basis.
Although Defendants are correct in noting that the pH solubility requirement
is one of the ways the patentees distinguished the prior art, it is not the only way.
As discussed above in construing the solubility requirement in the context of claim
59
1, the patentees also distinguished the prior art based on the thickness of the oral
dosage form coating which the patentees treated as a distinct concept in the
specification. Thus, I am not persuaded by Defendants’ argument that the patentees’
criticism of non-pH based carrier systems (such as time-release based systems) in the
prior art means that a pH limitation must be imported in all claims.
Indeed, such a conclusion would be contrary to Federal Circuit precedent that
“when a patent claim does not contain a certain limitation and another claim does,
that limitation cannot be read into the former claim in determining either validity or
infringement.” Amgen Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1326
(Fed. Cir. 2003) (internal citation marks omitted). There is a rebuttable presumption
that “different claims are of different scope.”
Id.; In re Katz Interactive Call
Processing Patent Litig., 639 F.3d 1303, 1313 (Fed. Cir. 2011).17 Defendants have
not pointed to intrinsic or extrinsic evidence sufficient to overcome that presumption
here. To the contrary, the prosecution history makes clear that the patentees
intended for claim 7 to be distinct from claim 1; the patentees explicitly stated in the
1996 responsive amendment in the divisional application that claim 7 differs from
claim 1 in that the pH solubility requirement is absent. File History, 08/401,696
App., Mar. 13, 1996 Responsive Amendment at 3 (Ainsworth Decl., Exh. O at
WC179).
17
While that presumption is especially strong when it relates to a dependent
and independent claim, see SunRace Roots Enterprise Co., Ltd. v. SRAM Corp., 336
F.3d 1298, 1303 (Fed. Cir. 2003), the presumption is likewise applicable to two
independent claims.
60
While the question whether claim 7 is enabled and/or invalid is a question to
be resolved on another day, that claim 7 does not provide for a carrier system by
which the dosage form will release to the right side of the colon raises a substantial
question in the Court’s mind as to whether the claim is enabled. Nevertheless, for
claim construction purposes it is clear that the patentees did not intend for claim 7
to include a solubility requirement.
Defendants further point to the following prosecution history language from the
same responsive amendment: “The composition of Claim [7] is embodied in the
product Asacol®.” Id. at 3. Defendants argue that, by using “is”, the patentees
intended to designate Asacol® as “the” sole embodiment of this claim—not just a
preferred embodiment. As such, Defendants argue, the scope of the claim must be
limited to the coating used for Asacol®, which is Eudragit S. Defendants rely on
Edwards Lifesciences LLC v. Cook Inc., 582 F.3d 1322 (Fed. Cir. 2009), for the
proposition that “when the preferred embodiment is described in the specification as
the invention itself, the claims are not necessarily entitled to a scope broader than
that embodiment.” Id. at 1330 (quoting Chimie v. PPG Indus. Inc., 402 F.3d 1371,
1379 (Fed. Cir. 2005)).
When read in context, the aforesaid language does not support Defendants’
contention that the patentees described Asacol® as the sole embodiment of claim 7
or that the patentees described Asacol® as “the present invention.” In context, the
statement reads:
61
[T]he question presented is whether the definition of the
coating as being such as to release the 5-amino-salicylic
acid, salt, or ester to the right side of the colon,
distinguishes [certain] Prior Art . . . The composition of
Claim [7] is embodied in the product Asacol®. As indicated
in the response of November 17, 1995, Laursen, et al., Gut
31, 1271-1276 (1990) describes Asacol® as tablets of 5amino-salicylic acid coated with Eudragit S and states that
most tablets have been shown to break up in the terminal
ileum or ascending colon and Fig. 7 of Stolk, et al. shows
that once the coating is removed from Asacol®, the 5-aminosalicylic acid (5-ASA) dissolves very quickly. . . . There is no
5-ASA held in reserve; all the 5-ASA is released. . . . It is
submitted that Claim [7] distinguishes Said Prior Art
combination because the provision of active ingredient
release profile in an oral dosage form whereby the oral
dosage form releases the 5-ASA to the right side of the colon,
is unobvious.
Id. at 3-4 (emphasis in original). This passage makes clear that, first of all, the
patentees were addressing the “so as to release the 5-amino-salicylic acid, salt, or
ester to the right side of the colon” language—not the solubility requirement. Second,
the patentees distinguished Asacol® from prior art by noting that it releases of all of
the 5-ASA in the colon without holding any 5-ASA in reserve. In this context, “[t]he
composition of Claim [7] is embodied in the product Asacol®” statement serves to
introduce the patentees’ reliance on Asacol® for illustrative purposes. Nothing in this
passage suggests that Asacol® is the sole embodiment of claim 7. Thus, Defendants’
reliance on Edwards is misplaced.18
18
Defendants’ reliance is further misplaced because Edwards interpreted
language in the specification, which is usually entitled to more weight than prosecution
history statements. See Phillips, supra at 1316 (describing the specification as “the
single best guide to the meaning of a claim term”).
62
Although I reject Defendants’ claim construction, I do not suggest that their
argument lacks intuitive force. As I noted in connection with my analysis of the
mixtures of Eudragit S and Eudragit L limitation, there are statements that, when
read in isolation, support Defendants’ arguments.
For example, in the 1996
responsive amendment, the patentees describe Asacol® as “representing the
invention.” File History, 08/401,696 App., Mar. 13, 1996 Responsive Amendment at
8 (Ainsworth Decl., Exh. O at WC184). Critically, however, the patentees did not
state that Asacol® was the only representation of the invention. Throughout the
amendment, the patentees present Asacol® as an example, perhaps, the prime
example. But there is nothing in the prosecution history language foreclosing the
possibility of additional embodiments. I am further convinced of this by recalling that
this responsive amendment is part of the divisional application. As explained supra,
the purpose of the divisional application that resulted in the ‘170 patent was to secure
broader claims. To read the patentees’ statements narrowly would be to ignore the
application of which the amendment was a part.
In this connection, I note that Defendants point to the Federal Circuit’s decision
in Alloc, Inc. v. International Trade Com'n, 342 F.3d 1361 (Fed. Cir. 2003), arguing
that the patentees may not recapture through the 1996 responsive amendment what
they allegedly disavowed early in the prosecution history and in the specification.
Alloc, however, did not involve a divisional application that created a larger context
within which to interpret the patentees’ subsequent incorporation of broader claims.
Moreover, in Saunders, supra, the Federal Circuit distinguished Alloc in a manner
63
relevant here. The specification in Saunders criticized prior art cylinders based on
their lack of pressure seals, noting that those cylinders “typically” could not maintain
adequate traction force. However, because the specification did not state that the use
of pressure seals was the “only way” to maintain traction force, the circuit concluded
that the specification did not support a narrowing construction. Saunders, 492 F.3d
at 1333. Likewise, here, although the specification disparages non-pH-based carrier
systems, the specification does not state that pH-based systems are the only means
by which the 5-ASA may be released to the right side of the colon.19
Accordingly, I construe claim 7 consistently with the manner in which I
construed claim 1, and not including the additional limitation proposed by
Defendants:
said solid oral dosage form being coated so that
substantially all of the 5-ASA leaves the dosage form in the
ascending colon and no amount of the 5-ASA is released
prior to the dosage form reaching the distal ileum.
19
Alloc is further distinguishable on its facts. The patent in that case
involved flooring products and methods for installing those products. In importing a
limitation that there be “play” between the components of the locking joints in the
flooring products, the court reasoned that the specification in that case taught “that the
invention as a whole, not merely a preferred embodiment, provides for play in the
positioning of the floor panels.” 342 F.3d at 1369. Here, by contrast, the Eudragit S
coating is a preferred embodiment. In addition, there was express language in the
prosecution history describing “[t]he claimed ‘play’ [as] of the present invention.” Id.
at 1371. As noted above, no such “present invention” language is present (pun
intended) here.
64
I reject Defendants’ attempt to incorporate a solubility requirement or language
limiting claim 7 to Eudragit S coatings into the construction.20
IV.
CONCLUSION
For the foregoing reasons, the Court adoptions the following claims
constructions.
Disputed Terms
A layer which is insoluble in gastric
juice and in intestinal juice below pH
7 but soluble in colonic intestinal
juice (Claim 1)
Construction
A layer of which no more than 0.01% of that layer
dissolves in gastric or intestinal juices below pH 7, but
does dissolve or disintegrate in colonic intestinal juice.
Whereby the dosage form releases the Whereby substantially all of the 5-ASA reliably leaves
5-amino-salicylic-acid, salt or ester to the dosage form in the ascending colon and no amount
the right side of the colon (Claim 1)
of the 5-ASA is released prior to the dosage form
reaching the distal ileum.
Whereby the 5-amino-salicylic-acid is
released to the right side of the colon
(Claim 6)
(same)
Said oral dosage form being coated so
as to release the 5-amino-salicylic-acid,
salt or ester to the right side of the
colon (Claim 7)
Said solid oral dosage form being coated so that
substantially all of the 5-ASA leaves the dosage form in
the ascending colon and no amount of the 5-ASA is
released prior to the dosage form reaching the distal
ileum.
20
Plaintiffs further argue that it would be impermissible for the Court to
limit a claim to Eudragit S, a trademarked drug name. I need not address this
argument as I reject the Eudragit S limitation for the reasons stated supra.
65
Date: June 1, 2012
/s/ Freda L. Wolfson
Freda L. Wolfson, U.S.D.J.
66
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