United States District Court, D. Delaware
GLAXOSMITHKLINE LLC and SMITHKLINE BEECHAM (CORK) LIMITED, Plaintiffs,
GLENMARK PHARMACEUTICALS INC., USA, Defendant. GLAXOSMITHKLINE LLC and SMITHKLINE BEECHAM (CORK) LIMITED, Plaintiffs,
TEVA PHARMACEUTICALS USA, INC., Defendant.
REPORT AND RECOMMENDATION
CHRISTOPHER J. BURKE UNITED STATES MAGISTRATE JUDGE.
these two related actions filed by Plaintiffs GlaxoSmithKline
LLC and SmithKline Beecham (Cork) Limited (collectively,
"GSK" or "Plaintiffs") against Defendant
Glenmark Pharmaceuticals Inc., USA ("Glenmark") and
Teva Pharmaceuticals USA, Inc. ("Teva")
(collectively, "Defendants"), GSK alleges induced
infringement of United States Patent No. RE40, 000 (the
"Asserted Patent" or the "'000
patent"). Presently before the Court is Defendants'
motion for summary judgment of invalidity (the
"Motion"). (Civil Action No. 14-877-LPS- CJB
(hereinafter "Glenmark Action"), D.I. 214;
Civil Action No. 14-878-LPS-CJB (hereinafter
"Teva Action"), D.I. 248) The Court
recommends that Defendants' Motion be DENIED.
manufactures and sells the drug carvedilol under the trade
name COREG®. (D.I. 60 at ¶¶ 8, 22) Plaintiff
SmithKline Beecham (Cork) Limited is the owner, by
assignment, of the '000 patent, which relates to methods
of administering carvedilol; Plaintiff Glaxo SmithKline LLC
is the patent's exclusive licensee. (Id. at
¶¶ 37-38; see also '000 Patent)
are engaged in the business of developing, manufacturing, and
distributing generic versions of branded drug products
throughout the United States. (See, e.g., Glenmark
Action, D.I. 61 at ¶ 47; Teva Action, D.I. 60
at ¶ 47; D.I. 105 at ¶ 47)
Discovery of Carvedilol as a Treatment for Congestive Heart
heart failure (or "CHF"), which has been construed
by the Court to mean "a condition that occurs as a
result of impaired pumping capability of the heart and is
associated with abnormal retention of water and
sodium[J" (D.I. 165 at 43), affects over 5 million
people in the United States, (D.I. 298 (hereinafter,
"McCann Decl. Vol. I"), ex. 2 at ¶ 23).
Symptoms of CHF include dyspnea (breathlessness), poor
exercise intolerance, fatigue and edema (swelling of the
legs). (D.I. 253 (hereinafter, "Rosendorff Decl."),
ex. A at ¶ 28; McCann Decl. Vol. I, ex. 2 at ¶ 24)
Historically, approximately half of the people that developed
CHF died within 5 years of diagnosis. (See '000
patent, col. l:55-57; McCann Decl. Vol. I, ex. 2 at ¶ 23)
Before 1997, the only treatments approved by the United
States Food and Drug Administration ("FDA") for
heart failure were diuretics, certain angiotensin converting
enzyme ("ACE") inhibitors and digoxin/digitalis.
(McCann Decl. Vol. I, ex. 2 at ¶ 25) These drugs were
used to treat the symptoms of heart failure. (Id.)
Controlled clinical trials also demonstrated that ACE
inhibitors reduced the risk of mortality from heart failure
by about 20%. (Id.)
has been a known beta blocker since at least 1978. (U.S.
Patent No. 4, 503, 067; see also McCann Decl. Vol.
I, ex. 2 at ¶ 29) Beta blockers are compounds that
prevent stimulation of the adrenergic receptors responsible
for increased heart rate and contractility, and thus they can
cause the heart to pump slower or with less force. (McCann
Decl. Vol. I, ex. 2 at ¶ 27) Historically, beta blockers
were contraindicated in the treatment of CHF because of the
medical community's "widely-held concern" that
this type of drug would further reduce the diseased and/or
damaged heart's ability to pump blood through the body.
(Id. at ¶¶ 27-28; see also D.I.
299 (hereinafter, "McCann Decl. Vol. IT), ex. 53 at 50,
55 (Glenmark's expert Sean C. Beinart, M.D. noting that
when he was in medical school in the "mid-'90s"
he was taught "capital letters, beta blockers are
contraindicated [for CHF]"); '000 patent, col. 3:56-
60) For example, guidelines published in 1993 regarding the
treatment of high blood pressure indicated that beta blockers
were "[r]elatively or [a]bsolutely
[c]ontraindicated" in patients with cardiac failure.
(McCann Decl. Vol. I, ex. 3 at Table 8; see also
GSK's Anticipation and Obviousness Presentation, Slide
dating back to the mid-1970s, groups were studying the
effectiveness of beta blockers to treat patients with CHF. In
1975, a group of Swedish researchers hypothesized that beta
blockers could "influence the progression of congestive
cardiomyopathy and prolong life in these patients[, ]"
(D.I. 264 (hereinafter, "Riley Decl. Vol. I"), ex.
3 at 1034-35), and by 1979, they published their first
clinical trial which "suggested that [beta blockers]
prolong survival in patients with congestive
cardiomyopathy[, ]" (id., ex. 4 at 1374-75;
cf. ex. 5 at ¶ 269). A study published in 1994
by Japanese physicians noted that "[e]vidence for the
effectiveness of long-term [beta blockers] in the treatment
of heart failure has been increasingly accumulated" and
concluded that the survival rate in patients with dilated
cardiomyopathy was significantly improved by beta-blocker
therapy. (Id., ex. 6 at 355-58)
carvedilol, in particular, the prior art included studies
showing that it improved hemodynamics and symptoms in
patients with CHF. (See, e.g., id., ex. 5 at
¶¶ 245-47, 293, 302; Rosendorff Deck, ex. A at
¶¶ 147-52, 156-58) For instance, an abstract
published in early 1993 described a study of carvedilol in 54
patients with CHF due to either idiopathic or ischemic
dilated cardiomyopathy; the abstract concluded that
"[c]arvedilol is well tolerated and improves both
symptoms and cardiac function in [such patients]."
(Riley Decl. Vol. I, ex. 7; see also Rosendorff
Deck, ex. A at ¶ 156) That same year, a researcher from
Australia, Dr. David T. Kelly, published an article that (1)
described recent studies that "have demonstrated
symptomatic improvement with carvedilol in patients with
heart failure" and (2) summarized a planned
"multicentre trial" (which was known as the
"ANZ pilot study" and was conducted by another
physician, Dr. Norman Sharpe) "to evaluate [the
drug's] efficacy and safety" (hereinafter, the
"Kelly reference" or "Kelly"). (Riley
Decl. Vol. I, ex. 8 (hereinafter,
"Kelly"); see also D.I. 297 at 13, 17n.12)
late 1980s, meanwhile, the named inventors of the '000
patent (Mary Ann Lukas-Laskey, Robert Ruffolo, Jr., and Neil
Howard Shusterman of GSK's predecessor and Gisbert Sponer
and Klaus Strein of Boehringer Mannheim Pharmaceuticals
Corporation) were investigating the possible uses of
carvedilol (then in development as a drug to treat
hypertension) to treat different diseases. (McCann Decl. Vol.
I, ex. 2 at ¶ 30; '000 patent, col. 3:15-36) They
pursued promising research suggesting that carvedilol could
be used to successfully treat CHF, receiving approval from
the FDA to initiate a clinical trial in 1992. (McCann Decl.
Vol. I, ex. 2 at ¶ 30) According to Dr. Ruffolo, the
reaction from his colleagues was very negative, due to
concerns that a beta blocker like carvedilol would actually
hasten the death of those with CHF. (McCann Decl. Vol. II,
ex. 81 at GSK00983250) One colleague told him that he was
'"going to kill a lot of people with that
drug[.]'" (Id.) GSK's Chief Executive
Officer received a letter protesting the studies of
carvedilol in CHF patients as resembling '"the
studies done by the Nazi scientists in the death camps of
World War II[.]'" (Id.; see also McCann
Decl. Vol. I, ex. 4 at 86) In light of these concerns, GSK
established a Data and Safety Monitoring Board
("DSMB") to monitor the trial and to stop it if
carvedilol, in fact, was killing patients. (McCann Decl. Vol.
I, ex. 4 at 87)
February 1995, the DSMB did indeed terminate the clinical
trial early, but based on the finding of a significant effect
of carvedilol on survival in CHF patients. (Id.;
see also id., ex. 2 at ¶ 33; id., ex. 6;
id., ex. 7; id., ex. 8 at 329-30) The trial
revealed that patients treated with carvedilol had an
approximately 65% lower risk of death than those given
placebo. (Id., ex. 11 at GSK00776812; see also
id., ex. 8 at 243-44; '000 patent, col. 3:60-64) In
light of this data, the DSMB believed that it would be
"'unethical'" to maintain a placebo arm of
the study. (McCann Decl. Vol. I., ex. 6-7; see also
id., ex. 4 at 87) The results of the clinical trial were
published in The New England Journal of Medicine.
(Id., ex. 11)
November 1995, GSK sought FDA approval of carvedilol to
reduce the risk of mortality caused by heart failure.
(Id., ex. 13 at ¶ 34) The FDA initially
rejected GSK's application, but after receiving
additional confirmatory data and analysis, in May 1997, the
FDA ultimately approved carvedilol as the first beta blocker
for the treatment of CHF, as an adjunctive therapy.
(Id. at ¶¶ 34-35; see also D.I.
297 at 5-6) The next month, GSK launched COREG. (McCann Decl.
Vol. I, ex. 14 at ¶ 10)
2004, the FDA had approved COREG for three indications:
1.1 Heart Failure: COREG® is indicated for the treatment
of mild-to-severe chronic heart failure of ischemic or
cardiomyopathic origin, usually in addition to diuretics, ACE
inhibitors, and digitalis, to increase survival and, also, to
reduce the risk of hospitalization...
1.2 Left Ventricular Dysfunction Following Myocardial
Infarction: COREG is indicated to reduce cardiovascular
mortality in clinically stable patients who have survived the
acute phase of a myocardial infarction and have a left
ventricular ejection fraction of <40% (with or without
symptomatic heart failure)...
1.3 Hypertension: COREG is indicated for the management of
essential hypertension . It can be used alone or in
combination with other antihypertensive agents, especially
(D.I. 60, ex. F at 1160) In 2006-2007 (and prior to the entry
into the market of Defendants' generic carvedilol in
September 2007), sales of COREG peaked at approximately $1.6
billion per year. (See McCann Decl. Vol. II, ex. 82
at GSK00983295; see also D.I. 297 at 6) And by 2007,
treatment guidelines specifically recommended carvedilol for
treatment of heart failure. (McCann Decl. Vol. I, ex. 13 at
¶ 50) Dr. Ruffolo and Dr. Lukas have received a number
of awards for their work in developing the invention claimed
in the '000 patent. (Id. at ¶¶ 381-83;
McCann Decl. Vol. II, ex. 82)
1995, the inventors filed a patent application directed to a
method of using carvedilol to decrease the risk of mortality
caused by CHF; the patent issued in June 1998 as U.S. Patent
No. 5, 760, 069 (the '"069 patent"), entitled
"Method of Treatment for Decreasing Mortality Resulting
from Congestive Heart Failure." (See '000
patent) The FDA published the '069 patent in the
"Approved Drug Products with Therapeutic Equivalence
Evaluations" publication (the "Orange Book")
as covering COREG for use in decreasing mortality caused by
CHF. (See McCann Decl. Vol. I, ex. 15)
November 2003, GSK requested a reissue of the '069
patent, and on January 8, 2008, that patent reissued as the
'000 patent. ('000 patent) In February 2008, GSK
replaced the '069 patent in the Orange Book with the
'000 patent, and it identified "Decreasing Mortality
Caused By Congestive Heart Failure" as the method of use
covered by the '000 patent that should be included as the
"use code" in that publication. (McCann Decl. Vol.
I, ex. 16 at GSK00592204, GSK00592217)
'000 patent contains 9 method claims directed to methods
of decreasing mortality caused by CHF in a patient in need
thereof by administering carvedilol in a manner recited in
the claims. ('000 patent) GSK asserts all but claim 5
against Defendants in these actions. (D.I. 249 at 3) Claim 1
is the only independent claim of the '000 patent, and it
1. A method of decreasing mortality caused by congestive
heart failure in a patient in need thereof which comprises
administering a therapeutically acceptable amount of
carvedilol in conjunction with one or more other therapeutic
agents, said agents being selected from the group consisting
of an angiotensin converting enzyme inhibitor (ACE), a
diuretic, and digoxin,
wherein the administering comprises administering to said
patient daily maintenance dosages for a maintenance period to
decrease a risk of mortality caused by congestive heart
failure, and said maintenance period is greater than six
('000 patent, col. 8:30-40 (emphasis in original)) The
italicized portion of the claim is the portion that was added
during the reissue proceeding.
limitations "decreasing mortality caused by congestive
heart failure" and "to decrease a risk of mortality
caused by congestive heart failure" will be referred to
herein as the "decreasing mortality limitations."
The Court has construed the decreasing mortality limitations
as claim limitations that mean '" attempting] to
reduce the probability that a patient will die as a result of
congestive heart failure.'" (D.I. 165 at 43-44;
see also D.I. 290 at 6-7)
3, 2014, GSK commenced these actions. (Glenmark
Action, D.I. 1; Teva Action, D.I. 1) GSK alleges
that Defendants induce infringement of the '000 patent by
making, offering to sell, selling, importing, and otherwise
promoting and distributing generic carvedilol tablets.
(Glenmark Action, D.I. 59, 175; Teva
Action, D.I. 60, 211) On October 16, 2014, Chief Judge
Leonard P. Stark referred these cases to the Court to hear
and resolve all pretrial matters, up to and including the
resolution of case-dispositive motions. (Glenmark
Action, D.I. 16; Teva Action, D.I. 18) After a
Markman hearing, (Glenmark Action, D.I.
118; Teva Action, D.I. 147), the Court issued a
Report and Recommendation on claim construction on June 3,
2016, (Glenmark Action, D.I. 133; Teva
Action, D.I. 165). Chief Judge Stark overruled objections to
that Report and Recommendation on February 17, 2017 as to all
but one term ("maintenance dosages").
(Glenmark Action, D.I. 251; Teva Action,
on the instant Motion was completed on March 3, 2017, (D.I.
313), and the Court held oral argument on the Motion (and
various other summary judgment and Daubert motions
filed in the case) on March 24, 2017, (D.I. 335 (hereinafter,
"Tr.")). A 5-day trial is set to begin in the
Teva Action on June 12, 2017. (D.I. 38, 329)
STANDARD OF REVIEW
of summary judgment is appropriate where "the movant
shows that there is no genuine dispute as to any material
fact and the movant is entitled to judgment as a matter of
law." Fed.R.Civ.P. 56(a). The moving party bears the
burden of demonstrating the absence of a genuine issue of
material fact. See Matsushita Elec. Indus. Co., Ltd. v.
Zenith Radio Corp., 475 U.S. 574, 585-86 & n.10
(1986). If the moving party meets this burden, the nonmovant
must then "come forward with specific facts showing that
there is a genuine issue for trial." Id. at 587
(emphasis in original) (internal quotation marks and citation
omitted). If the nonmoving party fails to make a sufficient
showing on an essential element of its case with respect to
which it has the burden of proof, the moving party is
entitled to judgment as a matter of law. Celotex Corp. v.
Catrett, 477 U.S. 317, 322-23 (1986). During this
process, the Court will "draw all reasonable inferences
in favor of the nonmoving party, and it may not make
credibility determinations or weigh the evidence."
Reeves v. Sanderson Plumbing Prods., Inc., 530 U.S.
133, 150 (2000).
in order to defeat a motion for summary judgment, the
nonmoving party must "do more than simply show that
there is some metaphysical doubt as to the material
facts." Matsushita, 475 U.S. at 586; see
also Podobnik v. U.S. Postal Serv., 409 F.3d 584, 594
(3d Cir. 2005) (party opposing summary judgment "must
present more than just bare assertions, conclusory
allegations or suspicions to show the existence of a genuine
issue") (internal quotation marks and citation omitted).
The "mere existence of some alleged factual
dispute between the parties will not defeat an otherwise
properly supported motion for summary judgment; the
requirement is that there be no genuine issue of
material fact." Anderson v. Liberty Lobby,
Inc., 477 U.S. 242, 247-48 (1986) (emphasis in
original). Disputes over facts that could alter the outcome
are "material, " and a factual dispute is genuine
only where "the evidence is such that a reasonable jury
could return a verdict for the nonmoving party."
Id. at 248. "If the evidence is merely
colorable, ... or is not significantly probative, ... summary
judgment may be granted." Id. at 249-50
(internal citations omitted). A party asserting that a fact
cannot be-or, alternatively, is-genuinely disputed'must
support the assertion either by citing to "particular
parts of materials in the record, including depositions,
documents, electronically stored information, affidavits or
declarations, stipulations (including those made for purposes
of the motion only), admissions, interrogatory answers, or
other materials"; or by "showing that the materials
cited do not establish the absence or presence of a genuine
dispute, or that an adverse party cannot produce admissible
evidence to support the fact." Fed.R.Civ.P. 56(c)(1)(A)
patent granted by the United States Patent and Trademark
Office (the "PTO") is presumed to be valid. 35
U.S.C. § 282(a); Microsoft Corp. v. i4i Ltd.
P'ship, 131 S.Ct. 2238, 2245-46 (2011). The
rationale underlying this presumption of validity is that
"the PTO, in its expertise, has approved the
claim[.]" KSR Int'l Co. v. Teleflex lnc,
550 U.S. 398, 426 (2007). The burden of proving invalidity
rests with the patent challenger at all times, who, when
disputed questions of fact arise, must establish a
patent's invalidity by clear and convincing evidence in
order to prevail. Microsoft Corp., 131 S.Ct. at
2245-49; see also Id. at 2253 (Breyer, J.,
concurring). Clear and convincing evidence places within the
mind of the fact finder "an abiding conviction that the
truth of [the] factual contentions are highly probable."
Procter & Gamble Co. v. Teva Pharms. USA, Inc.,
566 F.3d 989, 994 (Fed. Cir. 2009) (quoting Colorado v.
New Mexico, 467 U.S. 310, 316 (1984)). When a defendant
attempts to rely on prior art that was before the patent
examiner during prosecution in challenging the validity of a
patent, its burden is "especially difficult[.]"
Glaxo Grp Ltd. v. Apotex, Inc., 376 F.3d 1339, 1348
(Fed. Cir. 2004) (citation omitted).
is anticipated under 35 U.S.C. § 102(a) or (b) if:
(a) the invention was known or used by others in this
country, or patented or described in a printed publication in
this or a foreign country, before the invention thereof by
the applicant for patent, or
(b) the invention was patented or described in a printed
publication in this or a foreign country or in public use or
on sale in this country, more than one year prior to the date
of the application for patent in the United States ....
35 U.S.C. § 102. A patent claim is anticipated if each and
every limitation is found, either expressly or inherently, in
a single prior art reference. In re Gleave, 560 F.3d
1331, 1334 (Fed. Cir. 2009) (citing Eli Lilly & Co.
v. Zenith Goldline Pharms., Inc., 477 F.3d 1369, 1375
(Fed. Cir. 2006)); Moba, B.V. v. Diamond Automation,
Inc., 325 F.3d 1306, 1321-22 (Fed. Cir. 2003). This test
mirrors, to some extent, the test for infringement, and
"it is axiomatic that that which would literally
infringe if later anticipates if earlier."
Bristol-Myers Squibb Co. v. Ben Venue Labs., Inc.,
246 F.3d 1368, 1378 (Fed. Cir. 2001). In order to anticipate,
however, a reference must enable one of skill in the art to
make and use the invention without undue experimentation,
In re Gleave, 560 F.3d at 1334 (citing Impax
Labs., Inc. v. Aventis Pharms. Inc., 545 F.3d 1312, 1314
(Fed. Cir. 2008)), and must also "show all of the
limitations of the claims arranged or combined in the same
way as recited in the claims[, ]" Net MoneyIN, Inc.
v. VeriSign, Inc., 545 F.3d 1359, 1370 (Fed. Cir. 2008).
is a question of fact. Smith Kline Beecham Corp. v.
Apotex Corp., 403 F.3d 1331, 1343 (Fed. Cir. 2005). If
there are no genuine disputes underlying the anticipation
inquiry, then the issue is ripe for judgment as a matter of
this Motion, Defendants move for summary judgment on the
ground that the asserted claims of the '000 patent (i.e.,
all claims except for claim 5) are invalid because: (1)
claims 1-3 and 6-9 are anticipated by Kelly; and (2)
claims 4, 6 and 7 are obvious based on Kelly in combination
with other ...