Shire ViroPharma Incorporated v. CSL Behring LLC
Filing
237
MEMORANDUM OPINION. Signed by Judge Mitchell S. Goldberg on 11/18/2019. (lak)
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IN THE UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF DELAWARE
SHIRE VIROPHARMA INCORPORATED
Plaintiff,
v.
CSL BEHRING LLC and CSL BEHRING
GMBH
Defendants.
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CIVIL ACTION
NO. 17-414
Goldberg, J.
November 18, 2019
MEMORANDUM OPINION
In this patent infringement case, Plaintiff Shire ViroPharma Incorporated (“Plaintiff”)
alleges that Defendants CSL Behring LLC and CSL Behring GMBH (collectively, “Defendants”)
have, through the development and marketing of their drug HAEGARDA®, infringed multiple
patents owned by Plaintiff. Plaintiff originally alleged infringement of U.S. Patent No. 9,616,111
(the “’111 patent”), the claims of which I have already construed. Plaintiff subsequently alleged
infringement of four additional patents—U.S. Patent Nos. 10,080,788 (the “’788 patent”),
10,105,423 (the “’423 patent”), 10,130690 (the “’690 patent”), and 10,201,595 (the “’595”
patent)—which share the same specification as the ’111 patent and which are collectively known
as the “Continuation Patents.”
The parties now seek construction of three of the Continuation Patents’ disputed terms
pursuant to Markman v. Westview Instruments, Inc., 52 F.3d 967, 976 (Fed. Cir. 1995), aff’d, 517
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U.S. 370 (1996). The disputed claim terms are construed as indicated in this Memorandum and
accompanying Order. 1
I.
FACTUAL BACKGROUND
A. Hereditary Angioedema
Hereditary angioedema (“HAE”) is a rare genetic disorder causing insufficient natural
production of functional or adequate amounts of a protein called C1 esterase inhibitor (“C1-INH”).
This protein helps to regulate several complex processes involved in immune system function and
fibrinolytic system function. HAE exists in two forms. Type I occurs where the individual
produces either no or low C1-INH. Type II is present where the individual has the normal amount
of C1-INH, but it does not properly function. (Sec. Am. Compl. ¶ 12.)
Patients suffering from HAE experience symptoms including unpredictable, recurrent
attacks of swelling commonly affecting the hands, feet, arms, legs, face, abdomen, tongue,
genitals, and larynx. Currently, there are approximately 6,500 people in the United States who
suffer from this condition. (Id.)
HAE may be treated by administration of a drug containing a C1 esterase inhibitor in order
to restore the levels of C1-INH to levels sufficient to prevent or reduce the frequency or severity
of HAE attacks. HAE can be treated either acutely—meaning immediate treatment of an HAE
attack in order to slow it down or stop it altogether, or prophylactically—meaning administration
of a medication on a regular basis to prevent attacks. (Id. ¶ 13.)
1
On May 18, 2017, Chief Judge D. Brooks Smith of the United States Court of Appeals for
the Third Circuit designated me as a visiting judge for the District of Delaware, pursuant to 28
U.S.C. § 292(b), to handle this and other Delaware cases.
2
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B. The Patents-in Suit
1. The ’788 patent
On September 25, 2018, the United States Patent and Trademark Office (“PTO”) issued
the ’788 patent, entitled “C1-INH Compositions and Methods for the Prevention and Treatment of
Disorders Associated With C1 Esterase Inhibitor Deficiency.” The claims of the ’788 patent are
directed generally to
[A] method for prophylactic treatment of hereditary angioedema
(HAE) comprising subcutaneously administering . . . a
pharmaceutical composition comprising C1 esterase inhibitor,
sodium citrate, and having a pH ranging from 6.5–8.0, wherein the
C1 esterase inhibitor has a concentration of about 500 U/mL . . .
[The administration of the composition] increases the level of the
C1 esterase inhibitor in the blood of the subject to at least about 0.4
U/mL, [and the] C1 esterase inhibitor comprises the amino acid
sequence of residues 23 to 500 of SEQ ID NO: 1, [which amino acid
sequence is identified in the ’788 patent.]
Plaintiff is the assignee and owner of all rights, title, and interest in the ’788 patent.
(Id. ¶¶ 20–
22.)
2. The ’423 Patent
On October 23, 2018, the PTO issued the ’423 patent, entitled “C1-INH Compositions and
Methods for the Prevention and Treatment of Disorders Associated With C2 Esterase Inhibitor
Deficiency.” The claims of the ’423 patent are directed generally to
[A] pharmaceutical composition comprising C1 esterase inhibitor,
sodium citrate, and having a pH ranging from 6.5–8.0, wherein the
C1 esterase inhibitor comprises the amino acid sequence of residues
23 to 500 of SEQ ID NO: 1, [which amino acid sequence is
identified in the ’423 patent.]
Plaintiff is the assignee and owner of all rights, title, and interest in the ’423 patent. (Id. ¶¶ 23–
25.)
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3. The ’690 Patent
On November 20, 2018, the PTO issued the ’690 patent, entitled “C1-INH Compositions
and Methods for the Prevention and Treatment of Disorders Associated With C1 Esterase Inhibitor
Deficiency.” The claims of the ’690 patent are directed generally to
[A] pharmaceutical composition comprising C1 esterase inhibitor,
sodium citrate, and having a pH ranging from 6.5–8.0, wherein the
C1 esterase inhibitor has a concentration of about 400–600 U/mL,
and wherein the C1 esterase inhibitor comprises the amino acid
sequence of residues 23 to 500 of SEQ ID NO: 1, [which amino acid
sequence is identified in the ’690 patent.]
Plaintiff is the assignee and owner of all rights, title and interest in the ’690 patent. (Id. ¶¶ 26–28.)
4. The ’595 Patent
On February 12, 2019, the PTO issued the ’595 patent, entitled “C1-INH Compositions
and Methods for the Prevention and Treatment of Disorders Associated With C1 Esterase Inhibitor
Deficiency.” The claims of the ’595 patent are directed generally to
[A] method for prophylactic treatment of hereditary angioedema
(HAE) comprising subcutaneously administering . . . a
pharmaceutical composition comprising C1 esterase inhibitor,
sodium citrate, and having a pH ranging from 6.5–8.0, wherein the
C1 esterase inhibitor has a concentration of about 400–600 U/mL .
. . . [The administration of the composition] increases the level of
the C1 esterase inhibitor in the blood of the subject to at least about
0.4 U/mL, [and the] C1 esterase inhibitor comprises the amino acid
sequence of residues 23 to 500 of SEQ ID NO: 1, [which amino acid
sequence is identified in the ’595 patent.]
Plaintiff is the assignee and owner of all rights, title, and interest in the ’595 patent. (Id. ¶¶ 29–
31.)
C.
Defendants’ Alleged Infringement
On or about July 25, 2017, Defendants began U.S. sales of HAEGARDA®, a prophylactic
C1 esterase inhibitor treatment for subcutaneous administration, which received FDA approval on
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June 22, 2017. Plaintiff alleges that Defendants’ manufacture, importation, use, sale, and/or offer
to sell HAEGARDA in the United States directly infringes, induces others to infringe, and/or
contributorily infringes, either directly or under the doctrine of equivalents, one or more claims of
the Continuation Patents. (Id. ¶¶ 32–100.)
D.
Procedural History
On April 11, 2017, Plaintiff filed a patent infringement action against Defendants—under
Civil Action No. 17-414. In connection with that action, and by way of Memorandum and Order
dated January 18, 2019, I construed two terms: (1) the phrase “treating hereditary angioedema”
and (2) the phrase “increases the level of C1 esterase inhibitor in the blood of the subject up to
about 1 U/mL.”
Subsequently, on September 25, 2018, the PTO issued the ’788 patent to Plaintiff, which
is a continuation of the ’111 patent. Plaintiff filed a new complaint in this matter on the same
day—under Civil Action No. 18-1476—alleging that Defendants’ HAEGARDA product also
infringed at least claim 1 of the ’788 patent. The PTO then issued two other continuation
applications: the ’423 patent (October 23, 2018) and the ’690 patent (November 20, 2018).
Following a status conference, I directed that Plaintiff file an amended complaint in Civil Action
No. 18-1476.
Plaintiff filed its First Amended Complaint on January 7, 2019, alleging infringement of at
least claim 1 of the ’788 patent, the ’423 patent, and the ’690 patent. The PTO then indicated that
a fourth continuation patent—the ‘595 patent—would issue on February 12, 2019. The parties
agreed that Plaintiff would file a second amended complaint to include the ’595 patent. As noted
above, the Second Amended Complaint sets forth four counts of infringement, one for each of the
four Continuation Patents (’788, ’423, ’690, and ’595).
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On January 24, 2019, I administratively closed Civil Action No. 18-1476 and consolidated
it with the original action under Civil Action No. 17-414.
Currently pending are claim construction issues with respect to the Continuation Patents.
There are three terms in dispute. 2
II.
STANDARD OF REVIEW
The first step in a patent infringement analysis is to define the meaning and scope of the
claims of the patent. Markman, 52 F.3d at 976. Claim construction, which serves this purpose, is
a matter of law exclusively for the court. Id. at 979. “‘[T]here is no magic formula or catechism
for conducting claim construction.’ Instead, the court is free to attach the appropriate weight to
appropriate sources ‘in light of the statutes and policies that inform patent law.’” SoftView LLC
v. Apple Inc., No. 10-389, 2013 WL 4758195, at *1 (D. Del. Sept. 4, 2013) (quoting Phillips v.
AWH Corp., 415 F.3d 1303, 1324 (Fed. Cir. 2005)).
“It is a bedrock principle of patent law that the claims of a patent define the invention to
which the patentee is entitled the right to exclude.” Phillips, 415 F.3d at 1312 (internal quotation
marks omitted). The focus of a court’s analysis must therefore begin and remain on the language
of the claims, “for it is that language that the patentee chose to use to ‘particularly point[ ] out and
distinctly claim[ ] the subject matter which the patentee regards as his invention.’” Interactive Gift
Express, Inc. v. Compuserve, Inc., 256 F.3d 1323, 1331 (Fed. Cir. 2001) (quoting 35 U.S.C. § 112,
¶ 2). The terms used in the claims bear a “heavy presumption” that they mean what they say and
have their ordinary and customary meaning. Texas Digital Sys., Inc. v. Telegenix, Inc., 308 F.3d
2
At the claim construction hearing, five terms were in dispute. By letter dated November
13, 2019, the parties advised the Court that two of the disputes had been resolved, leaving only
three terms left for construction. (ECF No. 236.) Those three terms are the subject of this
Memorandum Opinion.
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1193, 1202 (Fed. Cir. 2002). That ordinary meaning “is the meaning that the term would have to
a person of ordinary skill in the art in question at the time of the invention, i.e., as of the effective
filing date of the patent application.” Phillips, 415 F.3d at 1313.
Generally, a person of ordinary skill in the art would not understand the ordinary and
customary meaning of a claim term in isolation. As such, the ordinary meaning may be derived
from a variety of sources including intrinsic evidence, such as the claim language, the written
description, drawings, and the prosecution history; as well as extrinsic evidence, such as
dictionaries, treatises, or expert testimony. Dow Chem. Co. v. Sumitomo Chem. Co., Ltd., 257
F.3d 1364, 1373 (Fed. Cir. 2001).
The “most significant source” of authority is “the intrinsic evidence of record, i.e., the
patent itself, including the claims, the patent specification 3 and, if in evidence, the prosecution
history.” Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996); see also
Phillips, 415 F.3d at 1313 (holding that a person of ordinary skill in the art is deemed to read the
claim terms in the context of the entire patent, including the specification). The specification “is
the single best guide to the meaning of a disputed term” and is usually dispositive as to the meaning
of words. Vitronics, 90 F.3d at 1582. Although it is improper to import limitations from the
specification into the claims, “one may look to the written description to define a term already in
a claim limitation, for a claim must be read in view of the specification of which it is a part.”
Renishaw PLC v. Marposs Societa’ per Azioni, 158 F.3d 1243, 1248 (Fed. Cir. 1998). On
occasion, “the specification may reveal a special definition given to a claim term . . . that differs
3
The specification is “that part of a patent application which precedes the claim and in which
the inventor specifies, describes, and discloses the invention in detail.” McCarthy’s Desk
Encyclopedia of Intellectual Property 408 (2d ed. 1995).
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from the meaning it would otherwise possess. In such cases, the inventor’s lexicography governs.”
Phillips, 415 F.3d at 1316. The specification may also “reveal an intentional disclaimer, or
disavowal, of claim scope by the inventor . . . [, which] is regarded as dispositive.” Id. “The
construction that stays true to the claim language and most naturally aligns with the patent’s
description of the invention will be, in the end, the correct construction.” Renishaw, 158 F.3d at
1250.
The court “should also consider the patent’s prosecution history, if it is in evidence.”
Markman, 52 F.3d at 980. This consists of “the complete record of proceedings before the Patent
Office and includes the prior art cited during examination.” Phillips, 415 F.3d at 1317. “Like the
specification, the prosecution history provides evidence of how the [Patent and Trademark Office]
and the inventor understood the patent.” Id. at 1317. Nonetheless, it is the least probative form of
intrinsic evidence because it “represents an ongoing negotiation between the PTO and the
applicant, rather than the final product of that negotiation.” Id.
If ambiguity still exists after considering all the intrinsic evidence, the court may rely on
extrinsic evidence, which is “all evidence external to the patent and prosecution history, including
expert and inventor testimony, dictionaries, and learned treatises.” Markman, 52 F.3d at 980.
“[D]ictionaries, and especially technical dictionaries, . . . have been properly recognized as among
the many tools that can assist the court in determining the meaning of particular terminology.”
Phillips, 415 F.3d at 1318. Additionally, expert testimony can provide background on the
technology at issue, explain how it works, speak to what a person of ordinary skill in the art would
understand, and establish that a particular term has a particular meaning in the pertinent field. Id.
Notably, however, extrinsic evidence is “less significant than the intrinsic record in determining
‘the legally operative meaning of claim language.’” C.R. Bard, Inc. v. U.S. Surgical Corp., 388
8
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F.3d 858, 862 (Fed. Cir. 2004) (quoting Vanderlande Indus. Nederland BV v. Int’l Trade Comm’n,
366 F.3d 1311, 1318 (Fed. Cir. 2004)).
Ultimately, during claim construction, “[t]he sequence of steps used by the judge in
consulting various sources is not important; what matters is for the court to attach the appropriate
weight to be assigned to those sources in light of the statutes and policies that inform patent law.”
Phillips, 415 F.3d at 303.
III.
DISCUSSION
The claim terms of the Continuation Patents in dispute are: (1) “prophylactic treatment of
hereditary angioedema,” (2) “pharmaceutical composition,” and (3) “the administration of the
composition increases the level of C1 esterase inhibitor in the blood of the subject to at least about
0.4 U/mL.” 4
A. “Prophylactic Treatment of Hereditary Angioedema”
The first disputed claim term is the phrase “prophylactic treatment of hereditary
angioedema,” which appears in claim 1 of both the ’788 patent and the ’595 patent. Plaintiff
offers the following construction:
[T]reatment administered to HAE patients at regular intervals before
an attack, resulting in avoiding future HAE attacks or reducing the
frequency and/or severity of future attacks.
Defendants’ alternative proposed construction is:
[T]reatment resulting in a decrease in the probability that the subject
will develop HAE or HAE attacks.
The distinctions between the parties’ proposals are three-fold. First, Plaintiff seeks to
define “prophylactic treatment” as treatment designed to avoid future HAE attacks or reduce the
4
These terms are used in various claims of the Continuation Patents. My construction of
the claim terms applies to all of the Continuation Patents in which they are used.
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frequency or severity of future attacks, whereas Defendants want to define “prophylactic
treatment” as decreasing the possibility of developing the condition of HAE or the onset of HAE
attacks. Second, Plaintiff suggests limiting “prophylactic treatment” to administration of the drug
at “regular intervals.” Defendants oppose this construction. Third, Plaintiff’s proposed definition
refers to HAE “patients,” whereas Defendants’ proposed definition refers to HAE “subjects.” I
address each of these arguments individually.
1.
Whether “Prophylactic Treatment” Includes Avoiding Future HAE Attacks or
Reduction in the Frequency or Severity of Future Attacks
As an initial point of reference, I turn to the specification and any relevant definitions.
“The specification is the single best guide to the meaning of a disputed term.” Pressure Prods.
Med. Supplies, Inc. v. Greatbatch Ltd., 599 F.3d 1308, 1314–15 (Fed. Cir. 2010) (quotations
omitted). “When a patentee explicitly defines a claim term in the patent specification, the
patentee’s definition controls.” Martek Biosicences Corp. v. Nutrinova, Inc., 579 F.3d 1364, 1380
(Fed. Cir. 2009).
The Continuation Patents at issue contain no express definition of “prophylactic
treatment.” However, two other definitions found within the ’788 and the ’595 patents are
instructive.
First, both patents provide a definition of the related term “prevent,” which references
“prophylactic treatment.” “Prevent” is defined as:
The prophylactic treatment of a subject who is at risk of developing
a condition (e.g., HAE or HAE attack) resulting in a decrease in the
probability that the subject will develop the condition.
(’788 Patent, col. 6, lines 32–35; ’595 Patent, col. 6, lines 33–36 (emphasis added).) Defendants
suggest that the term “prevent” is interchangeable with the term “prophylactic treatment.” I
disagree because the express term used in claim 1 of the patents is “prophylactic treatment of
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hereditary angioedema,” not “prevention of heredity angioedema.”
Thus, while the term
“prophylactic treatment” is contained within the definition of “prevent,” a claim construction of
“prophylactic treatment” cannot be limited to the definition of “prevent.”
Both the ’788 and the ’595 patents also define the term “treat,” which is part of the term
“prophylactic treatment.” According to that definition:
The term “treat” as used herein refers to any type of treatment that
imparts a benefit to a patient afflicted with a disorder, including
improvement in the condition of the patient (e.g., in one or more of
the symptoms), delay in the progression of the condition, etc. In a
particular embodiment, the treatment of HAE results in at least a
reduction in the severity and/or number of HAE attacks.
(’788 patent, col 6, lines 36–43; ’595 patent, col. 6, lines 37–43.)
My prior claim construction of the ’111 patent defined the term “treating” as “[a]ny type
of treatment that imparts a benefit to a patient afflicted with HAE, including improvement in the
condition of the patient (e.g., in one or more symptoms), delay in the progression of the condition,
etc. In a particular embodiment, the treatment of HAE results in at least a reduction in the severity
and/or number of HAE attacks.” 5 Shire ViroPharma, Inc. v. CSL Behring, LLC, No. 17-414, 2019
WL 266327, at *5 (D. Del. Jan. 18, 2019). Importantly, I also concluded that “prophylactic
treatment” was a subset of “any type of treatment” and involved “at least a reduction in the severity
and/or number of HAE attacks.” Id. at *5–6.
Reading the definitions of “prevent” and “treat” together, in conjunction with my prior
construction of “treating,” suggests that proper construction of the term “prophylactic treatment”
5
“[W]e presume, unless otherwise compelled, that the same claim term in the same patent
or related patents carries the same construed meaning.” Omega Eng’g, Inc, v. Raytek Corp., 334
F.3d 1314, 1334 (Fed. Cir. 2003); see also AstraZeneca AB v. Andrx Labs, LLC, Nos. 14-8030,
15-1057, 2017 WL 111928, at *10 (D.N.J. Jan. 11, 2017) (“[T]he interpretations of the same or
other district courts are generally considered to be highly relevant and persuasive authority.”).
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lies somewhere in the middle of these terms. On one hand, “prophylactic treatment” is narrower
than the definition term “treat” and encompasses the “reduction in the severity and/or number of
HAE attacks.” On the other hand, “prophylactic treatment” appears to fully subsume the definition
of “prevent”—which is “prophylactic treatment” resulting in the “decrease in the probability that
the subject will develop the condition [HAE or HAE attacks]”—but the term is not clearly limited
to just that definition.
For further guidance, I also look to the dependent claims of the Continuation Patents, which
are a second source of intrinsic evidence. “Other claims of the patent in question, both asserted
and unasserted, can . . . be valuable sources of enlightenment . . . [b]ecause claim terms are
normally used consistently throughout the patent . . . .” Phillips, 415 F.3d at 1314. “Differences
among claims can also be a useful guide . . . For example, the presence of a dependent claim that
adds a particular limitation gives rise to a presumption that the limitation in question is not present
in the independent claim.” Id. at 1314–15. This “presumption is especially strong when the
limitation in dispute is the only meaningful difference between an independent and dependent
claim, and one party is urging that the limitation in the dependent claim should be read into the
independent claim.” SunRace Roots Enter. Co., Ltd. v. SRAM Corp., 336 F.3d 1298, 1303 (Fed.
Cir. 2003). “[A] dependent claim cannot be broader than the claim from which it depends.” Alcon
Research, LTD v. Apotex Inc., 687 F.3d 1362, 1367 (Fed. Cir. 2012). In other words, “independent
claims . . . must be at least as broad as the claims that depend from them.” AK Steel Corp v. Sollac
& Ugine, 344 F.3d 1234, 1242 (Fed. Cir. 2003).
In the patents-in-suit, dependent claim 20 describes, “[t]he method of claim 1, wherein
administration of the composition results in at least a reduction in the severity and/or number of
HAE attacks.” (’788 patent, col. 14, lines 32–34; ’595 patent, col. 14, lines 32–34.) As a
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dependent claim cannot be broader from the independent claim from which it depends, it stands to
reason that the method of claim 1—which references “prophylactic treatment”—must include
treatment that “results in at least a reduction in the severity and/or number of HAE attacks.” See
Trustees of Columbia Univ. in City of New York v. Symantec Corp., 811 F.3d 1359, 1370 (Fed.
Cir. 2016) (“[I]n a situation where dependent claims have no meaningful difference other than an
added limitation, the independent claim is not restricted by the added limitation in the dependent
claim.”); Merck Sharp & Dohme Corp. v. Hospira Inc., 221 F. Supp. 3d 497, 520 (D. Del. 2016)
(declining to adopt a construction that would exclude a dependent claim from the scope of the
claim from which it depends).
Defendants assert that defining the term “prophylactic treatment” in independent claim 1
to be equivalent to language in independent claim 20 is problematic under the fundamental tenet
of claim construction in that “the presence of a dependent claim that adds a particular limitation
gives rise to a presumption that the limitation in question is not present in the independent claim.”
(Defs.’ Opening Claim. Constr. Br. 14 (quoting Phillips, 415 F.3d at 1314–15).) Defendants
reason that to construe “prophylactic treatment” as used in claim 1 of the ’788 and ’595 patents to
include “a reduction in the number and/or severity of attacks” would render dependent claim 20—
which is specifically limited to those results—superfluous.
This concern, however, is properly resolved by a construction that takes into account not
only “a reduction in the number and/or severity of future attacks”—as found in dependent claim
20—but also “a decrease in the probability that the subject will develop HAE or future HAE
attacks”—a phrase not in claim 20. Such a construction will render claim 1 broader than claim 20,
thereby avoiding the presumption against redundancy between independent and dependent claims.
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A construction that includes both “a reduction in the number and/or severity of future
attacks” and “a decrease in the probability that the subject will develop HAE or future HAE
attacks” finds support in a third source of guidance—the prosecution history, which “includes the
prior art cited during the examination of the patent.” Phillips, 415 F.3d at 1317. Like the
specification, the prosecution history may be useful in revealing either a special meaning assigned
by the patentee to the term or a disclaimer clarifying what the claims do not cover. Id. Prior art
references, particularly when cited in the specification or prosecution history “can often help to
demonstrate how a disputed term is used by those skilled in the art.” Vitronics Corp. v.
Conceptronic, Inc., 90 F.3d 1576, 1584 (Fed. Cir. 1996). Indeed, “[w]hen prior art that sheds light
on the meaning of a term is cited by the patentee, it can have particular value as a guide to the
proper construction of the term, because it may indicate not only the meaning of the term to persons
skilled in the art, but also that the patentee intended to adopt that meaning.” Arthur A. Collins,
Inc. v. N. Telecom Ltd., 216 F.3d 1042, 1045 (Fed. Cir. 2000); see also Ross-Hime Designs, Inc.
v. United States, 126 Fed. Cl. 299, 325 (Fed. Cl. 2016) (adopting, for purposes of claim
construction, the definition used in a prior art reference cited in the specification); Katz v. AT&T
Corp., 63 F. Supp. 2d 583, 591 (E.D. Pa. 1999) (“A court also may consider the prior art cited in
the prosecution history, which may contain clues as to what the claims do not cover.”).
Here, during prosecution of the Continuation Patents, Plaintiff cited multiple prior art
references that describe “prophylactic treatment of HAE” to include a reduction in the number and
severity of attacks. For example, in a patent application entitled “C1 Inhibitor Produced in the
Milk of Transgenic Mammals,” the term “prophylactic treatment” is used to describe the use of
“androgens or fibrinolytic agents . . . to reduce the number and severity of attacks.” (Pl.’s Opening
Claim Constr. Br., Ex. F, at Shire_0000265 (emphasis added).) In another referenced article,
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entitled “A Review of Hereditary Angioedema and Recombinant Human C1-Inhibitor Treatment,”
prophylactic treatments are described as treatments “that reduce the occurrence of attacks or
prevent the anticipated triggering of an attack.” (Pl.’s Opening Claim Constr. Br., Ex. H, at
Shire_0001516 (emphasis added).)
Synthesizing all of this intrinsic evidence and my prior claim construction, I conclude that
the term “prophylactic treatment,” as used in the Continuation Patents, should incorporate portions
of the definitions proposed by both parties. Consistent with the definition of “prevent” in the
specification—“prophylactic treatment” should include treatment resulting in a decrease in the
probability that the subject with develop HAE or future HAE attacks. And consistent with (a) the
definition of “treat” in the specification, (b) the dependent claims, and (c) the prosecution history—
“prophylactic treatment” should also include treatment that results in reducing the frequency or
severity of future HAE attacks.
2.
Whether “Prophylactic Treatment” Requires Administration at “Regular Intervals”
The parties have also asked me to construe whether the term “prophylactic treatment”
should include administration at “regular intervals.” Plaintiff urges the inclusion of the phrase
administration at “regular intervals” into the definition of “prophylactic treatment,” whereas
Defendants posit that this limitation has no foundation in the intrinsic evidence. For the following
reasons, I agree with Defendants on this issue.
As noted above, neither the terms “treat” nor “prevent” discuss the method of
administration of the C1 esterase inhibitor. Moreover, nothing in the specification injects a
limitation directed towards administration at “regular intervals before an attack.” To the contrary,
the specification discusses the use of dosing “at appropriate intervals” using permissive language:
The pharmaceutical preparation comprising the molecules of the
instant invention may be administered at appropriate intervals, for
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example daily, every other day, every three days, five out of every
7 days, or at least one two or three times a week or more until the
pathological symptoms are reduced or alleviated, after which the
dosage may be reduced to a maintenance level. The appropriate
interval in a particular case would normally depend on the condition
of the patient.
(’788 patent, col. 5, lines 39–47 (emphasis added); ’595 patent, col. 5, lines 39–47 (emphasis
added).) The dependent claims discuss various means in which the dosing may occur. For
example, dependent claims four through six appear to describe a single administration of the C1
esterase inhibitor, whereas claims seven through nine describe particular dosing intervals. (’788
Patent, col. 13, lines 32–38; ’595 patent, col. 13, lines 32–38.)
As Plaintiff has offered no support from either the intrinsic or extrinsic evidence suggesting
that “prophylactic treatment” requires dosing “at regular intervals,” I decline to include this
language in the construction of this term.
3.
“Patient” versus “Subject”
The final point of dispute on this claim term is whether “prophylactic treatment” involves
administration of the C1-INH to an HAE “patient” or to a “subject.”
In support of its use of the term “patient,” Plaintiff points to my original construction of
“treating HAE” in the ’111 patent, which I defined as “[a]ny type of treatment that imparts a benefit
to a patient afflicted with HAE, including improvement in the condition of the patient . . .” Shire,
2019 WL 266327, at *13 (emphasis added). As the phrase “prophylactic treatment” includes the
definition of “treating,” Plaintiff contends that the claim “prophylactic treatment” in the
Continuation Patents must also consistently use the word “patient.” Plaintiff further contends that
the remainder of the specification repeatedly describes the administration of the claimed
“pharmaceutical composition” to a “patient” and that the purpose of the invention is to “restor[e]
the levels of active C2 esterase inhibitor in these patients to or near normal levels.” (’788 and ’595
16
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patents, col. 1, lines 38–42; col. 2, lines 4–7, col. 5, lines 27–29; col. 5, lines 32–34 (emphasis
added).)
Plaintiff’s argument, however, disregards the fundamental tenet that claim construction
analysis begins “by considering the language of the claims themselves.” Trustees of Columbia
Univ. in City of New York v. Symantec Corp., 811 F.3d 1359, 1363 (Fed. Cir. 2016). Here, claim
1 of both the ’788 Patent and the ’595 Patent defines “[a] method of prophylactic treatment” of
HAE by “subcutaneously administering to a subject in need thereof” the C1 esterase inhibitor.
(’788 patent, col. 13, lines 13–16 (emphasis added); ’595 patent, col. 13, lines 12–14 (emphasis
added).) In describing the invention, the specification provides that “[i]n accordance with the
instant invention, compositions and methods for inhibiting (e.g., reducing or slowing), treating,
and/or preventing a disorder associated with C2 esterase inhibitor deficiency in a subject are
provided.” (’788 patent, col. 2, lines 18–21 (emphasis added); ’595 patent, col. 2, lines 18–21
(emphasis added).) Plaintiff has not explained the difference between the terms “patient” and
“subject” or why the actual claim language must be altered to substitute “patient” for “subject.”
As such, I decline to change the terminology used in the claim language. 6
For all of the reasons set forth above, I will construe the term “prophylactic treatment of
hereditary angioedema” as “treatment resulting in a decrease in the probability that the subject
will develop HAE or future HAE attacks, or reducing the number and/or severity of future HAE
attacks.”
6
To the extent Plaintiffs seek to substitute the term “patient” in for the term “subject” in any
other disputed claim, I reject such construction for the same reasons as set forth herein.
17
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B.
“Pharmaceutical Composition”
The next disputed claim term is the phrase “pharmaceutical composition,” which appears
in claim 1 of all four of the Continuation Patents. Plaintiff seeks to construe this phrase as meaning,
“a composition for administration to a patient,” while Defendants suggest “a liquid composition
for administration to a subject.” In short, Defendants seek to limit the claimed “composition” to
liquid form, while Plaintiff’s construction does not specify the form of the “composition.” For the
following reasons, I will adopt Plaintiff’s construction of this term.
In support of their added “liquid” limitation, Defendants contend that I must consider the
usage of the disputed claim term in the context of the claim as a whole. Abbott Labs. v. Syntron
Bioresearch, Inc., 334 F.3d 1343, 1351 (Fed. Cir. 2003). Defendants urge that the claim language
teaches a liquid composition because each of the independent claims of the Continuation Patents
requires that the “pharmaceutical composition” have a concentration expressed in U/mL.
According to Defendants, concentration refers “to the relative amount of a given substance, here
C1 esterase inhibitor, in a unit volume, here 1 milliliter.” (Defs.’ Opening Claim Constr. Br. 7
(citing Oxford Dictionary of Chemistry (4th ed. 2000)).) 7 Defendants explain that given the
inclusion of a particular concentration requirement expressed in Units per milliliter, a person of
ordinary skill in the art would understand the claimed pharmaceutical composition to be a liquid.
This analysis finds no support in either the claim language itself, the specification, or the
dependent claims.
First, the claim language neither expressly nor implicitly teaches a limitation to a liquid
pharmaceutical composition.
Rather, the claim describes “a pharmaceutical composition
7
“Dictionary definitions provide evidence of a claim term’s ‘ordinary meaning.’” Abbott
Labs., 334 F.3d at 1350.
18
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comprising C1 esterase inhibitor, sodium citrate, and having a pH ranging from 6.5–8.0, wherein
the C1 esterase inhibitor has a concentration of about 500 U/mL . . .” (’788 patent, claim 1; ’595
patent, claim 1; ’423 patent, claim 1, ’690 patent, claim 1.) Notably absent from this language is
any requirement that the “composition” be a liquid. The mere presence of a specified concentration
in the claim language does not mandate that the invention be in liquid form at the outset, but merely
requires that, prior to administration of the invention to a subject, such a concentration must exist.8
Defendants’ construction is also at odds with the specification. Here, the specification
explicitly provides that “[t]he pharmaceutical composition of the present invention can be
prepared, for example, in liquid form, or can be in dried powder form (e.g., lyophilized for later
reconstitution).” (’788 Patent, col. 4, lines 38–41.) 9 In other words, the specification clearly
describes both a liquid “pharmaceutical composition” and a solid/powder “pharmaceutical
composition.” It goes on to state that “[i]n a particular embodiment, the compositions are
formulated in lyophilized form. Where the compositions are provided in lyophilized form, the
compositions are reconstituted prior to use . . . by an appropriate buffer” including sterile water.
(Id., col. 4, lines 42–46.) Thus, to construe “pharmaceutical composition” as a liquid—as
Defendants
urge—would
render
meaningless
the
specification’s
statement
that
the
“pharmaceutical composition” could be a lyophilized powder that is later reconstituted.
Plaintiff’s construction also finds support within the doctrine of “claim differentiation,”
which “stems from ‘the common sense notion that different words or phrases used in separate
8
Defendants argue that the specification only determines what Plaintiff could have claimed,
not what it actually claimed. (Defs.’ Answering Claim Constr. Br. 6.) This argument, however,
disregards the fact that the claim language does not clearly indicate the form of the “pharmaceutical
composition,” notwithstanding its reference to a concentration of C1-INH measured as U/mL.
9
Where the specifications of the four Continuation Patents are identical, I will cite to only
one of the patents.
19
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claims are presumed to indicate that the claims have different meanings and scope.’” Seachange
Int’l, Inc. v. C-COR, Inc., 413 F.3d 1361, 1368 (Fed. Cir. 2005) (quoting Karlin Tech. Inc. v.
Surgical Dynamics, Inc., 177 F.3d 968, 971–72 (Fed. Cir. 1999)). The doctrine is at its strongest
“where the limitation sought to be read into an independent claim already appears in a dependent
claim.” Seachange, 413 F.3d at 1368–69 (quotations omitted). “To the extent that the absence of
such difference in meaning and scope would make a claim superfluous, the doctrine of claim
differentiation states the presumption that the difference between the claims is significant.”
Tandon Corp. v. U.S. Int’l Trade Comm’n, 831 F.2d 1017, 1023 (Fed. Cir. 1987).
The doctrine of claim differentiation renders the addition of any “liquid” limitation invalid.
Claim 16 of the ’423 and ’690 patents teaches, “[t]he pharmaceutical composition of claim 1,
wherein the pharmaceutical composition is prepared in liquid form.” (’423 patent, col. 14, lines
22–23; ’690 patent, col. 14, lines 14–15.) This dependent claim adds a limitation to those recited
in the independent claim. Curtiss-Wright Flow Control Corp. v. Velan, Inc., 438 F.3d 1374, 1380
(Fed. Cir. 2006) (stressing that “a dependent claim must add a limitation to those recited in the
independent claim”). To read “pharmaceutical composition” in claim 1 to mean a “liquid
composition” would make claim 16 superfluous to claim 1, in contravention of the doctrine of
claim differentiation. Stated another way, reading claim 1 without the limitation of “liquid” makes
dependent claim 16 appropriately narrower in scope than the independent claim from which it
depends.
Dependent claim 17 of the ’423 and ’690 patents reinforces this interpretation, as it teaches
“[t]he pharmaceutical composition of claim 1, wherein the pharmaceutical composition is
20
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reconstituted with water from at least one lyophilized powder.” 10 (’423 patent, col. 14, lines 24–
26; ’690 patent, col. 14, lines 16–18.) As noted above, “a dependent claim cannot be broader than
the claim from which it depends.” Alcon Research, LTD v. Apotex Inc., 687 F.3d 1362, 1367
(Fed. Cir. 2012). Thus, if claim 1 were limited to a “liquid pharmaceutical composition,”
dependent claim 17—which describes a “pharmaceutical composition” that starts as a lyophilized
powder and is then reconstituted with a liquid—would be excluded from the scope of claim 1. 11
Defendants also cite the prosecution histories of the Continuation Patents. Defendants
contend that, in response to obvious rejections during the prosecution of the ’788 and ’423 patents,
Plaintiff argued that “[t]here is ample evidence in the literature that details well-known
impediments with regard to converting intravenous dosing of a medicament to subcutaneous
dosing of a medicament.” (Defs.’ Opening Claim Constr. Br., Exs. 13 and 14.) These “wellknown impediments” in the literature referred to issues of “viscosity, solubility, and protein
aggregation”—problems associated with liquid compositions. (Id.) Based on these references,
10
Similarly, claim 2 of the ’788 patent teaches, “[t]he method of claim 1, wherein the
pharmaceutical composition is reconstituted with water from at least one lyophilized powder
comprising at least about 2000 U Cl esterase inhibitor and less than about 5000 U C1 esterase
inhibitor.” (’788 Patent, col. 13, lines 24–28.)
11
Defendants contend that if the claimed “pharmaceutical composition” includes lyophilized
powder, claim 17 of the ’423 and ’690 Patents would be rendered nonsensical because claim 17
would read “the [lyophilized powder] is reconstituted with water from at least one lyophilized
powder.” (Defs.’ Answering Claim Constr. Br. 9.) Plaintiff, however, does not seek to have
“pharmaceutical composition” defined as “lyophilized powder,” but rather as “the composition for
administration to a patient.” Using that definition, claim 17 would more coherently read, “the
[composition for administration to a patient] is reconstituted with water from at least one
lyophilized powder.”
Defendants also argue that the dependent claims do not describe solid and liquid
pharmaceutical compositions, but rather two methods of arriving at the claimed liquid
“pharmaceutical compositions.” That is, the claimed liquid compositions are either (1) made
directly in liquid form, or (2) prepared by reconstituting a lyophilized powder in liquid. Such an
interpretation is entirely inconsistent with the specification which, as discussed above, provides
that the “composition” itself can be in either liquid or dried powder form.
21
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Defendants argue that “[g]iven [Plaintiff’s] reliance on alleged difficulties in formulating liquid
pharmaceutical compositions to overcome the [PTO’s] obviousness rejections,” Plaintiff clearly
claimed only liquid compositions and “should not be allowed to expand its claim scope to
encompass solid pharmaceutical compositions.” (Defs.’ Opening Claim Constr. Br. 12.)
Defendants’ prosecution disclaimer argument is unavailing. Prosecution disclaimer is not
appropriate in instances “where the alleged disavowal of claim scope is ambiguous,” or where
remarks made by an inventor to overcome a rejection may be viewed “as amenable to multiple
reasonable interpretations.” Omega Eng’g, Inc. v. Raytek Corp., 334 F.3d 1314, 1324 (Fed. Cir.
2003) (citing N. Telecom Ltd. v. Samsung Elec. Co., 215 F.3d 1281, 1293–95 (Fed. Cir. 2000)).
Rather, “for prosecution disclaimer to attach, [Federal Circuit] precedent requires that the alleged
disavowing actions or statements made during prosecution be both clear and unmistakable.” Id.
at 1325–26; Cordis Corp. v. Medtronic Ave, Inc., 511 F.3d 1157, 1177 (Fed. Cir. 2008) (reiterating
that “arguments made to distinguish prior art references” will be considered disavowals “only if
they constitute clear and unmistakable surrenders of subject matter”).
Here, Plaintiff’s statements to the PTO during prosecution do not constitute a “clear and
unmistakable” limitation of the claimed “pharmaceutical composition” to a liquid form. Rather,
Plaintiff simply described for the PTO certain difficulties with subcutaneous products that are
present regardless of whether the “pharmaceutical composition” is originally in liquid form, or
whether it is originally in lyophilized powder form and then reconstituted into a liquid for purposes
of administering it to a subject through a syringe. As such, I do not find any clear prosecution
history disclaimer. 12
12
The parties also reference extrinsic evidence in support of their proposed constructions.
As I find that the meaning of this term is clear from the intrinsic record, I decline to consider this
evidence. See Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1578, 1583 (Fed. Cir. 1996) (“In
22
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For all of the reasons set forth above, I will construe “pharmaceutical composition” as “a
composition for administration to a subject.”
C.
“The Administration of the Composition Increases the Level of the C1
Esterase Inhibitor in the Blood of the Subject to at Least About 0.4 U/mL”
The final claim term in dispute is the language in independent claim 1 of the ’788 and ’595
patents: “the administration of the composition increases the level of C1 esterase inhibitor in
the blood of the subject to at least about 0.4 U/mL.” Plaintiff’s proposed construction adopts
this precise language, whereas Defendants seek to construe the term as meaning, “the
administration of the composition raises the level of active C1 esterase inhibitor in the blood of
the subject from below about 0.4 U/mL to at least about 0.4 U/mL or higher after administration
of the composition.” The parties’ dispute focuses on (1) Defendants’ use of the word “raises”
instead of “increases,” and (2) Defendants’ addition of “from below about 0.4 U/mL” and “or
higher” to the claim language.
The first portion of the dispute—the use of the word “raises” versus ”increases”—is easily
resolved because Defendants offer no basis for altering the explicit claim language. Indeed,
Defendants expressly concede that “raises” and “increases” are “wholly synonymous with one
another, and would be understood by a person having ordinary skill in the art as different means
of expressing the goal of the claimed inventions: restoration of active C1-INH blood levels.”
(Defs.’ Answering Claim Constr. Br. 17 n.4.) Given this concession, I will adopt the word
“increases,” as that is the term used in the actual claim language.
The second part of the dispute—Defendants’ addition of a baseline level of active C1
esterase inhibitor—requires a more in-depth analysis.
those cases where the public record unambiguously describes the scope of the patented invention,
reliance on any extrinsic evidence is improper.”).
23
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Again, I start with the claim language itself. The Federal Circuit has clarified that “[i]f we
need not rely on a limitation to interpret what the patentee meant by a particular term or phrase in
a claim, that limitation is ‘extraneous’ and cannot constrain the claim.” Renishaw PLC v. Marposs
Societa’ per Azioni, 158 F.3d 1243, 1249 (Fed. Cir. 1998). “It is improper for a court to add
‘extraneous’ limitations to a claim, that is, limitations added ‘wholly apart from any need to
interpret what the patentee meant by particular words or phrases in the claim.’” Hoganas AB v.
Dress Indus., Inc., 9 F.3d 948, 950 (Fed. Cir. 1993) (quoting E.I du Pont de Nemours & Co. v.
Phillips Petroleum Co., 849 F.2d 1430, 1433 (Fed. Cir. 1998)). Thus, “when a claim term is
expressed in general descriptive words, we will not ordinarily limit the term to a numerical range
that may appear in the written description or in other claims . . . Nor may we, in the broader
situation, add a narrowing modifier before an otherwise general term that stands unmodified in a
claim.” Renishaw, 158 F.3d at 1249.
Consistent with these principles, the language of the claim term here requires no
modification. 13 The claim provides that the administration of the composition “increases the level
of C1 esterase inhibitor in the blood of the subject to at least about 0.4 U/mL.” As set forth in my
prior claim construction opinion, the term “U/mL” refers to “the mean quantity of C1 inhibitor
activity present in 1 mL of normal human plasma.” Shire, 2019 WL 266327, at *18 (emphasis in
original). Simply put, the claim requires that once the composition is administered to a subject,
13
Defendants urge that Plaintiff has waived any objection to Defendants’ construction
because Plaintiff has not advanced a construction addressing the ordinary meaning of the term
“increases.” This argument is meritless. Plaintiff clearly proposed a construction of that claim
term in the joint claim construction statement and its briefing on claim construction. Simply
because Plaintiff’s proposed construction substantially adopts the language of the claim term
itself—language that seems to require no further construction—does not mean that Plaintiff has
waived its argument.
24
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the subject’s level of active C1 esterase inhibitor will be above “at least about” 0.4 U/mL. The
claim therefore includes not only subjects whose level of C1-INH is below 0.4 U/mL, but also
those subjects whose level is already at “about” 0.4 U/mL and needs to be increased. To add in
Defendants’ proposed language—that the subject’s “level of active C1 esterase inhibitor in the
blood” 14 must start “from below about 0.4 U/mL”—improperly injects a limitation not present in
the claim. 15
My construction finds ample support in the specification. The specification is silent on any
starting level of C1-INH in the subject and discusses solely what the C1-INH level should be after
administration of the composition.
When describing the background of the invention, the
specification clarifies that “restoring the levels of active C1 esterase inhibitor in these patients to
or near normal levels is an effective measure for treating HAE.” (’788 patent, col. 1, lines 39–42.)
14
Defendants’ citation to AztraZeneca AB v. Dr. Reddy’s Laboratories, Ltd., No. 05-5553,
2010 WL 11414548, at *13 (D.N.J. May 18, 2010) is inapposite. In that case, the court construed
the term “increased average plasma levels (AUC) per dosage unit” to mean “greater blood levels
of (-)-omeprazole . . . compared to the typical or usual blood levels for omeprazole.” Id. at *13.
The court found such a construction necessary because the claim term “increased average plasma
levels” provided no point of reference on which to determine what were “increased average plasma
levels.” Id.
By contrast here, the claim language provides a point of reference regarding what the term
“increase” means by noting that the level of active C1 esterase in the blood must “increase” to “at
least about 0.4 U/mL” regardless of where the C1-INH level started. Contrary to Defendants’
argument, Plaintiff’s refusal to accord any additional meaning to the term “increases” does not
violate any well-settled canons of claim construction.
15
Indeed, Defendants seem to concede that claim language is not in need of additional
construction. In their reply brief, they argue that, “Shire chose to limit its claims to methods where
subjects’ deficient C1-INH blood levels are increased to or above a specific level after
administration of the composition. The plain and ordinary meaning of ‘increases’ clearly contrasts
the post-administration blood level of ‘about 0.4 U/mL’ to the subjects’ C1-INH blood levels prior
to administration, which are below 0.4 U/mL.” (Defs.’ Reply Br. 7–8 (emphasis added).) Given
that the claim language is clear, and Plaintiff does not dispute that this is what it means,
Defendants’ additions are unnecessary.
25
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In other words, the focus is on achievement of a specific level of active C1-INH, not on a starting
point. The specification goes on to note that “[i]n a particular embodiment, the C1 esterase
inhibitor is administered with a frequency and dosage so as to increase the C1 esterase inhibitor
level to at least about 0.3, or more particularly, 0.4 U/mL or more up to about 1 U/mL . . . in the
blood of the subject.” (Id. col. 5, line 66–col. 6, line 4.) Repeatedly, the specification discusses
the desired maintenance of about 0.4 U/mL or higher for at least 50% of the time, suggesting that
a subject whose C1 esterase level starts at or above about 0.4 U/mL would still be included within
the claim. (Id. col. 6, lines 4–24.) Moreover, the specification’s reference to increasing a subject’s
C1 esterase inhibitor level “up to about 1 U/mL” indicates that the invention may be used to
increase a subject’s levels from some number above 0.4 U/mL to up to 1 U/mL. 16
Likewise, none of Defendants’ citations to the prosecution history support their proposed
construction. Defendants reference the Declaration of Dr. Jennifer Schranz, submitted to the PTO,
which opined that the invention teaches only the achievement of “an appropriate threshold of
functional C1-INH activity for routine prophylaxis” and “[p]redicts” the “concentration of
functional C1-INH in adult HAE patients receiving certain subcutaneous injections.” Dr. Schranz,
however, does not cite any baseline starting level. (Defs.’ Opening Claim Constr. Br., Ex. 16, ¶ 9
& Fig. 5.) 17 Defendants also reference the Patent Examiner’s Notice of Allowability for the ’595
16
Defendants make cursory reference to dependent claims 11–14 of the ’788 and ’595
patents, which prescribe “maintenance” of the blood levels achieved in independent claim 1 “at or
above 0.4 U/mL” for various time periods. Defendants claim that once the level of C1-INH in the
blood is raised “to” 0.4 U/mL, this level is maintained “at” 0.4 U/mL for a specified period.
Nothing in this argument supports construction of the term “increase” to require inclusion of an
original or base level of C1-INH in the blood of the subject.
17
Defendants argue that Figure 5 of Dr. Schranz’s declaration shows that adult HAE subjects’
C1-INH blood levels are below the “threshold level” of 0.4 U/mL prior to administration. (Id. at
Fig. 5.) This Figure, however, does not confine the open-ended scope of the claim terms. While
Dr. Schranz’s study tracked adults with starting C1-INH blood levels of below 0.4 U/mL prior to
26
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patent. That document, however, also supports Plaintiff’s construction, noting that “[t]he claims
are drawn to a method of prophylactic treatment of hereditary angioedema by administration of a
subcutaneous formulation . . . to raise the blood level of the inhibitor to at least about 0.4 U/mL.”
(Defs.’ Opening Claim Constr. Br., Ex. 17, at p. 3.) Again, no baseline level is included.
Finally, none of the prior art references submitted during prosecution—on which
Defendants now rely—teach the inclusion of a baseline level. (See, e.g,, Defs.’ Opening Claim
Constr. Br., Ex. 18, at 148 (noting that in the common form of the disease, the reduction in
functional activity is due to C1-INH concentrations being only 5–30% of normal, but “in the
variant form of the disease, immunochemically detectable concentrations of C1-INH are normal
or elevated, but a dysfunctional mutant protein is synthesized . . . . Furthermore, functional
inadequacy of C1-INH can be transient without any decrease in the level of C1-INH.”); Ex. 19, p.
907 (noting only that “for prevention of attacks, subphysiologic levels of C1-inhibitor (as low as
40% of normal levels) are sufficient”).) 18
administration, the claim language itself does not clearly impose a limitation requiring that subjects
have such a baseline level.
18
In a final effort to bolster their respective positions, both parties cite to extrinsic evidence.
Plaintiff specifically references a statement from their expert Andrew MacGinnitie. Dr.
MacGinnitie testified at his deposition that, for certain HAE patients, achievement of 0.4 U/mL
would not always result in treatment of an HAE attack. (Pl.’s Opening Claim Constr. Br., Ex. M,
Dep. of Andrew MacGinnitie, 117:15–23.)
Defendants quote a dictionary definition of “increase” from Webster’s Collegiate
Dictionary, noting that the term “increase” is defined as “to make greater.” (Defs.’ Opening Claim
Constr. Br., Ex. 20.) Defendants then posit that, to “make greater” requires that the starting point
be less than the end result.
I find no need to resort to this extrinsic evidence to properly construe the term “increases,”
as its meaning is unambiguous and clear from the intrinsic record. See Vitronics Corp. v.
Conceptronic, Inc., 90 F.3d 1578, 1583 (Fed. Cir. 1996) (“In those cases where the public record
unambiguously describes the scope of the patented invention, reliance on any extrinsic evidence
is improper.”).
27
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Accordingly, I will adopt Plaintiff’s proposed construction and define this term as “the
administration of the composition increases the level of C1 esterase inhibitor in the blood of the
subject to at least about 0.4 U/mL after administration of the composition.”
IV.
CONCLUSION
The claims shall be construed as set forth above and in the Claim Construction Order that
follows.
28
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