Appendix — Merck & Co. v. Teva Pharmaceuticals USA, Inc.
Supreme Court brief2005
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APPENDIXA
United States Court of Appeals for the Federal Circuit
04-1005
MERCK & CO., INC.,
Plaintiff-Appellee,
v.
TEVA PHARMACEUTICALS USA, INC..,
Defendant-Appellant.
DECIDED: January 28, 2005
Before RADER, GAJARSA, and PROST, Circuit Judges.
Opinion for the court filed by Circuit Judge GAJARSA.
Dissenting opinion filed by Circuit Judge RADER.
GAJARSA, Circuit Judge.
Teva Pharmaceuticals USA, Inc. (“Teva”) appeals the
final judgment of the United States District Court of
Delaware, which, after a bench trial, found Merck & Co.'s
(“Merck”) U.S. Patent No. 5,994,329 (issued Nov. 30, 1999)
(“the '329 patent”) not invalid as anticipated or obvious. The
district court further found the '329 patent to be enforceable,
and the '329 patent claims 23 and 37 constructively infringed
by Teva's Abbreviated New Drug Application (“ANDA”)}
under 35 U.S.C. § 271 (e)(2)(A) of the Hatch-Waxman Act.
Merck & Co.. Inc. v. Teva Pharms. USA, Inc., 288 F. Supp.
2a
2d 601 (D. Del. 2003) (“Merck”); Merck & Co., Inc. v. Teva
Pharms. USA, Inc., No. 01-CV-0048, Order (D. Del. Sept.
24, 2003) (Final Judgment Order Pursuant to Fed. R. Civ. P.
54(b)) (’Einal Judgment Order”). '
We disagree with the district court's construction of
the claim term “about” in claims 23 and 37 of the '329 patent.
Because we further hold claims 23 and 37 obvious in light of
the prior art. we vacate the judgment of the district court and
hold the claims invalid and not infringed.
L. BACKGROUND
A. “329
Merck owns the "329 patent. The '329 patent, entitled
“Method for Inhibiting Bone Resorption,” teaches a method
of treating and preventing osteoporosis through less-than-
daily administration of bisphosphonate ‘compounds. ‘329
patent. col. 1. Il. 15-25. The patent was filed on August 14,
1998. and Merck stipulated at trial that it would not allege an
invention date prior to July 22, 1997 for the claims at issue.
Merck. 288 F. Supp. 2d at 606.
Bisphosphonates are a family of chemical compounds
that are known to selectively inhibit the bone destruction
process that contributes to osteoporosis and other bone
diseases. “329 patent, col. 1, II. 45-50. Bisphosphonates
include. among other compounds, alendronate, risedronate,
tiludronate, pamidronate, ibandronate, zolendronate, and
etidronate. Id. at col. 1, II. 54-65; col. 2, I]. 28-31. At issue in
On appeal, Teva does not challenge the district court's determination
that the 329 patent is enforceable or that it would be infringed by Teva's
proposed drug product.
3a
this case are once-weekly dosages of alendronate
monosodium trihydrate.
Bisphosphonates are not readily absorbed by the
gastrointestinal (“GI”) tract. The medications thus require
rigorous dosing instructions: a patient must take the medicine
on an empty stomach and remain upright and fasting for
thirty minutes after ingestion. '329 patent, col. 2, II. 3-24. In
addition, the compounds are known to have adverse Gl side
effects that physicians believed to be related, in part, to (a)
irritation to the patient's esophagus, or (b) the size of the
dose. Id at col. 2, II. 23-46.
Before the '329 patent issued, standard osteoporosis
treatments consisted of small daily doses of bisphosphonates
to avoid GI complications. Id, at col. 1, II. 54-61; col. 2, I.
34-35, 44-46. According to the patent, however, the adverse
GI side-effects resulting from repetitive irritation to the Gl
tract were the primary concern in the field. Id. at col. 2, Il.
65-67; col. 3, I. 57 - col. 4, L. 13. The inventors trumpeted the
reduced-frequency dosing schedule disclosed in the ‘329
patent as decreasing the irritating effect of the compounds, as
well as increasing patient compliance with the ngorous
dosing instructions. Id. at col. 3, [1. 57-64; col. 4, II. 14-23.
This case involves dependent claims 23 and 37 of the
‘329 patent. At trial, the parties agreed to cast the text of these
claims in independent form, incorporating all the dependent
limitations:
23. A method for treating osteoporosis in
human comprising orally administering about 70
mg of alendronate monosodium trihydrate. on an
alendronic acid basis, as a unit dosage according to
a continuous schedule having a dosing interval of
once-weekly.
| 4a
37. A method for preventing osteoporosis in
human comprising orally administering about 35
mg of alendronate monosodium trihydrate, on an
alendronic acid basis, as a unit dosage according to
a continuous schedule having a dosing interval of
once-weekly.
'329 patent, col. 21, Il. 24-27 (claim 23) (emphasis added);
col. 22, Il. 24-26 (claim 37) (emphasis added). We note that
the only differences between claim 23 and claim 37 are (1)
the dosage amount of alendronate monosodium trihydrate (70
mg or 35 mg) and (2) whether the method is directed to
treating or preventing osteoporosis.
Merck has Food and Drug Administration (“FDA”)
approval to market both a once-weekly and a relatively
diminished daily dose of alendronate monosodium trihydrate,
which it does under the trade name Fosamax. Merck, 288 F.
Supp. 2d at 605.
B. _Litigat
In late 2000, Teva amended an existing ANDA and
sought FDA approval to market generic versions of Merck's
once-weekly Fosamax supplement in 35 mg and 70 mg
quantities.’ Merck, 288 F. Supp. 2d at 605-06; Teva Br. at 4.
Merck subsequently fiew suit against Teva under 35 U.S.C. §
? Teva filed one amendment for the once-weekly 70 mg dosage, and
later filed another for the once-weekly 35 mg dosage. Merck, 288 F.
Supp. 2d at 605-06. Merck separately sued Teva for infringement, under
35 U.S.C. § 271 (eX 2A), based on each ANDA amendment. Id. The
district court consolidated those suits in the present action.
Sa
271 (e)(2)A), alleging Teva's ANDA filing was an act of
infringement.”
According to the trial court, Merck acted as its own
ordinary meaning of “about” in claims 23 and 37 - which
both parties agree has the ordinary meaning “approximately”
- to something quite different. Merck, 288 F. Supp. 2d at 612-
16. Thus, the district court concluded the terms “about 35
mg” in claim 37 and “about 70 mg” in claim 23 mean exactly
35 (or 70) mg of alendronic acid.
Relying on this construction of “about,” the district
court dismissed Teva's allegations that the claims at issue
were (1) anticipated by a July 1996 Lunar News article or (2)
rendered obvious by an April 1996 Lunar News article
combined with the July 1996 article.’ The trial court found
> ‘The present case relates to another action between the two parties
involving Merck's daily formulation of Fosamax. The district court found
Teva's proposed generic daily alendronate compound would infringe
Merck's patent on that drug, and this court affirmed that decision. Merck
& Co. v, Teva Pharms. USA Inc., 347 F.3d 1367 (Fed. Cir. 2003). In this
action the parties agreed to be bound by the judgment from: this court on
issues relating to the daily formulation. As a result, the only issues before
the district court in this case related to the "329 patent. Merck, 288 F.
Supp. 2d at 606.
‘ ‘That is, the trial court construed “the disputed claim terms ‘about
70/35 mg’ to mean the equivalent of 70/35 mg of alendronic acid when
taking into account molecular weight variances for its derivatives that
carry accessories,” Merck, 288 F. Supp. 2d at 616.
> Lunar News is a quarterly newsletter distributed to approximately
15,000 to 20,000 physicians and others in the medical art by Lunar
Corporation, a manufacturer of bone densitometry equipment used to
diagnose osteoporosis. Merck, 288 F. Supp. 2d at 618-19, Teva Br. at 11-
12. The author of each article is Dr. Mazess, who has a doctorate degree
in anthropology, but does not have formal training in pharmacology. Id.
6a
both articles qualified as prior art publications under 35
U S.C. § 102¢a). Merck, 288 F. Supp. 2d at 618-19. The April
199% article in Lunar News recommends weekly dosages of
alendronate to improve patient compliance:
{O}ne of the difficulties with alendronate is its low
oral bioavailability. When taken with water in a
fasting state, only about 0.8% of the oral dose is
bioavailable. Even coffee or juice reduces this by
O06. and a meal reduces it by >85%. Alendronate
must be taken. after an overnight fast, 30-60
seated or standing: a very small group of patients
have reported some upper gastrointestinal distress if
this is not done. This regime may be difficult for the
elderly [to] maintain chronically. An intermittent
(pdate Bisphosphonate. Lunar News, Apr. 1996, at 31
(emphasis added).
The July 1996 Lunar News article further emphasizes
the need for a once-weekly dose of Fosamax because
“[slome United States physicians are reluctant to treat
[patients with Fosamax] because of: a) side effects; b)
difficulty of dosing: and c) high costs ($700/year).” The
author suggests:
Teva pommts out. however. that Dr Mazess directed the Bone Mineral
Lapormor, at the Unrversity of Wisconsin, established bone densitometry
= 2 Gagnosx wol founded the firs’ manufacturer of bone densitometry
meaowing egqupmem (Luna), was Lunar's first president, has
parucipaied © and designed cimucal tals for osteoporosis treatment, and
mn wider pubbshed m the bone disease field
Ta
The difficulties with oral bisphosphonates may
favor their episodic (once/week) or cyclical (one
week cach month) administration. Even oral
alendronate potentially could be given in a 40 or 80
mg_dose once/week to avoid dosing problems and
reduce
costs.
Update: Bisphosphonate, Lunar News, July 1996, at 23
(emphasis added).
Regarding anticipation, the trial court held the July
1996 article does not “expressly or inherently disclose the
dosage amounts for alendronate in claims 23 and 37” because
there was no evidence that 40 mg and 80 mg of alendronate
contains “the same number of alendronate core molecules” as
found in 35 mg and 70 mg, respectively, of alendronic acid.
Merck, 288 F. Supp. 2d at 618-20.
As for obviousness, the district court concluded the
suggestion of weekly treatment was not “clinically useful or
obvious in July 1997 because of the known dose-related
gastrointestinal side effects” associated with the daily
formulation of Fosamax. Merck, 288 F. Supp. 2d at 628.
Although it is undisputed that a once-weekly dosage was
known to be efficacious, the court determined that the Lunar
* Teva argues that the 40 mg and 80 mg amounts were recommended
because 40 mg tablets of alendronate monosodium trihydrate were
commercially available for those who suffer from Paget's disease. a bone
disorder that also responds to bisphosphonate treatment. The standard
daily dose of Fosamax is 5 mg or 10 mg. Exact multiples of the standard
daily dose corresponding to the amount of Fosamax administered in a
week, ie.. 35 mg or 70 mg. were not commercially available at the time
of the '1996 Lunar News articles. Thus, Teva argues, the 40 mg and 80 mg
dosages should be viewed as teaching the 329 patent's seven-foid
‘ncrease in daily dosages (5 and 10 mg) im terms of the 40 mg doses
then-available on the market.
8a
News articles could not overcome doctors’ concerns
associated with higher dosages because the Lunar News
articles were not published in peer-reviewed journals or
authored by one skilled in the art. Merck, 288 F. Supp. 2d at
628-29.
Finding the ‘329 patent not invalid as anticipated or
obvious, the district court delayed the effective date of the
FDA approval of Teva's ANDA until the '329 patent expires
and enjoined commercial sale of Teva's generic treatment.
Final Judgment Order at 1. This appeal followed. We have
jurisdiction under 28 U.S.C. § 1295(a)(1).
Il. DISCUSSION
A. Standard of Review
On appeal from a bench trial, this court reviews the
district court's conclusions of law de novo and findings of
fact for clear error. Golden Blount, Inc. v. Robert H.
Peterson Co., 365 F.3d 1054, 1058 (Fed. Cir. 2004); Brown
& Williamson Tobacco Corp. v. Philip Morris Inc., 229 F.3d
1120, 1123 (Fed. Cir. 2000). A finding is clearly erroneous
when, despite some supporting evidence, “the reviewing
court on the entire evidence is left with the definite and firm
conviction that a mistake has been committed.” United States
y. United States Gypsum Co., 333 U.S. 364, 395 (1948).
The court reviews claim construction, a question of
law, de novo. Cybor Corp. v. FAS Techs., Inc., 138 F.3d
1448, 1456 (Fed. Cir. 1998) (en banc). Obviousness is a
question of law based on underlying factual determinations.
Richardson- Vicks, Inc. v. Upjohn Co., 122 F.3d 1476, 1479
(Fed. Cir. 1997). The court reviews an obviousness ruling de
novo, but reviews the underlying factual findings for clear
error. Graham v. John Deere Co.. 383 U.S. 1, 17 (1966);
Golden Blount, 365 F.3d at 1058. The underlying factual
9a
determinations include (1) the scope and content of the prior
art, (2) the level of ordinary skill in the art, (3) the differences
between the claimed invention and the prior art, and (4)
objective indicia of nonobviousness. Graham, 383 U.S. at 17-
18.
B. Claim Construction
In finding that Merck acted as its own lexicographer,
the district court relied on the following passage from the
specification:
Because of the mixed nomenclature currently in use
by those or [sic] ordinary skill in the art, reference
to a _ specific weight or percentage of
bisphosphonate compound in the present invention
is on an active weight basis unless otherwise
‘329 patent, col. 10, I. 65 - col. 11, L. 8 (emphasis added).
According to the district court's opinion, the patentee uses the
phrase “about 35 [or 70] mg” to account for variations in the
molecular weight of the different derivatives of alendronic
acid and to deliver exactly 35 (or 70) mg of alendronic acid.
Merck, 288 F. Supp. 2d at 613. For example, the court noted
that alendronate monosodium trihydrate, which is used in
Fosamax, requires an atom of sodium for each molecule. Id.
at 613-14. If a heavier metal were chosen, such as potassium,
the weight of the derivative compound would have to
increase to deliver exactly the same number of molecules of
10a
the active alendronate compound found in 35 [or 70] mg of
alendronic acid. Id. at 614. The district court thus construed
the term “about 35 [or 70] mg™ to mean the amount of the
denvative compound that gives exactly 35 [or 70] mg of the
active compound.
We reverse the district court's construction of “about”
and hold that such term should be given its ordinary meaning
of “approximately.” To properly construe a claim term, a
court first considers the intrinsic evidence, starting with the
The dissent frames the dispute in terms of the entire phrase “about 70
[55] mg of alendronate monosodium trihydrate. on an alendronic acid
basts. ~ Post at 2:22-3.2. Notwithstanding this contention, the district court
entified the - -disputed claim terms” as “about 70 / 35 mg.” Merck, 288
F Supp. 2d at 616. In its brief to this court, Merck likewise stated the
issue as whether the distnct court property construed the aforementioned
limmation (not disputed term) on grounds that the "329 patent expressly
defined “about 70 mg™ as calculated “based on 76 mg of alendronic acid.”
See Appellee Br. at 3 (statement of issues). We agree with Merck, and the
distinct court. that the dispute concerns the proper meaning of “about.”
We thus understand the dissent to argue that meaning is fixed by the
comiex: of the claum and the language of the writter description.
it 1s correct to look first to those sources for the meaning at issue. See
Viromes. 90 F.3d at 1582. However. as is noted above when the intrinsic
evidence does not clearty establish its own lexicography, it is proper to
Getermime the ordmary meaning of the term. For that reason we ascribe
“about” ms ordmary meaning here.
Moreover. the dissent pursues a philosophical argument as to the
deference which should be given to the trial court. Claim construction
bemg 2 legal matier m is reviewed de novo and this is stil] the law
norwithstandime the desire of some members of this court to consider
crealmg am excepuon to that rule. See Cybor, 138 F.3d at 1462-63
Plager. J. comcurring). id at 1463-66 (Mayer, CJ., concurring in
jucgmenm j. 16 at 1473-75 (Rader, J, dissenting). Therefore, if we apply
proper iegal precedent as the majority has done in this case, the result is
jitc@ and obvious
language of the claims. Vitronics Corp. v. Conceptronic, Inc..
90 F.3d 1576, 1582 (Fed. Cir. 1996). Generally claim terms
should be construed consistently with their ordinary and
customary meanings, as determined by those of ordinary skill
in the art. Brookhill-Wilk 1, LLC v. Intuitive Surgical, Inc..
334 F.3d 1294, 1298 (Fed. Cir. 2003). While in some cases
there is a presumption that favors the ordinary meaning of a
term, Tex. Digital Sys. v. Telegenix Inc., 308 F.3d 1193, !202
(Fed. Cir. 2002), the court must first examine the
specification to determine whether the patentee acted as his
own lexicographer of a term that already has an ordinary
meaning to a person of skill in the art. See, ¢.g., Renishaw
PLC v. Marposs Societa’ per Azioni, 158 F.3d 1243, 1250
(Fed. Cir. 1988); Brookhill v. Wilk, 334 F.3d at 1299.
When a patentee acts as his own lexicographer in
redefining the meaning of particular claim terms away from
their ordinary meaning, he must clearly express that intent in
the written description. See, ¢.g., Bell Atl. Network Servs. v.
Covad Communications Group, Inc., 262 F.3d 1258, 1268
(Fed. Cir. 2001). We have repeatedly emphasized that the
statement in the specification must have sufficient clarity to
put one reasonably skilled in the art on notice that the
inventor intended to redefine the claim term. Id.; see also
Elekta Instrument S.A. v. O.U.R. Sci. Int'l, Inc., 214 F.3d
1302, 1307 (Fed. Cir. 2000) (“Absent an express intent to
impart a novel meaning, claim terms take on their ordinary
meaning.”); Renishaw, 158 F.3d at 1249 (“The patentee’s
lexicography must, of course, appear ‘with reasonable clarity,
deliberateness, and precision’ before it can affect the claim.”)
(quoting In re Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994)).
v
Co., 308 F.3d 1167, 1177-78 (Fed. Cir. 2002) (stating that the
“presumption in favor of the claim term's ordinary meaning
is overcome, however, if a different meaning is clearly and
deliberately set forth in the intrinsic evidence”). In the
12a
present case, the passage cited by the district court from the
specification for Merck's definition of “about” is ambiguous.
It fails to redefine “about™ to mean “exactly” in clear enough
terms to justify such a counterintuitive definition of “about.”
The phrase’s ambiguity arises from the fact that it can
easily be read as Teva does - as a way of explaining what is
meant by the use of the phrase “alendronate acid active
basis” rather than as a way of radically redefining what is
meant by “about.” The district court corstrued the phrase
“about 70 [or 35] mg™ to mean that one should administer
approximately 70 (or 35) mg of the derivative compound,
such that the end result is that the patient is administered
exactly 70 (or 35) mg of alendronic acid. In other words, the
district court determined that the quantity specified in the
claims (35 or 70 mg) modifies the amount of the derivative
compound rather than the active compound. Under such a
construction, the term “about” informs one of ordinary skill
in the art to select whatever quantity of the derivative
compound necessary to give exactly 35 (or 70) mg of
aiendronic acid: for alendronate monosodium trihydrate, the
word “about™ thus meant that 45.68 mg (or 91.35 mg) of that
compound should be delivered - the amount necessary to
give exactly 35 (or 70) mg of alendronic acid.
Unlike the limiting definition of “about” adopted by
the district court, Teva's interpretation of the paragraph in
question would mean that “70 [or 35] mg” refers to the
amoumt of the active compound to be administered rather
than the amount of the derivative compound. The term
“about™ in the claims would then serve to modify the quantity
of the active compound in a way consistent with its normal
definition of “approximately.” Under this construction, the
l3a
modifying phrase “about 70 [or 35] mg” would refer to
approximately 70 (or 35) mg of alendronic acid.*
The claim construction urged by Merck and adopted
by the district court reads the sentence of the passage
underlined above out of context. In the sentence before the
highlighted sentence, the patentee informs those of ordinary
skill in the art that, when the patent refers to a certain amount
of a bisphosphonate compound, it is actually instructing them
to administer a certain amount of the active component of the
compound rather than the compound itself, i.e., that one
should calculate the amount dispensed on an “active weight
basis.” This preceding sentence thus acts to specify a
common denominator to be used for all derivatives of
alendronic acid. The vnderlined sentence merely gives a
specific example - that of an alendronate derivative - to show
what is meant by using the phrase “active weight basis.”
Given that the passage that Merck relies on is
amenable to a second (and more reasonable) interpretation,
we hold Merck did not clearly set out its own definition of
“about” with “reasonable clarity, deliberateness, and
precision,” and thus failed to act as its own lexicographer. In
re Paulsen, 30 F.3d at 1480.
As further support for this conclusion, we note that
other parts of the specification also suggest that “about”
should be given its ordinary meaning of “approximately.”
The specification repeatedly describes a range of acceptable
° Merck argues that the district court's construction is supported by the
fact that “about” was not used twice in the underlined sentence cited by
Merck, i.e., that the specification does not state that “the amount of
bisphosphonate compound selected is calculated based on about 70 mg of
alendronic acid.” (emphasis added). While Merck's grammatical savvy is
noted, we believe that the omission of a second “about” is likely an
inadvertent error rather than the product of meticulous drafting.
l4a
dosage amounts, with the patentee emphasizing that unit
dosages will vary. For example, the specification suggests
that a once-weekly dosage amount could contain anywhere
from about 17.5 mg to about 70 mg of any alendronate
compound on an alendronate acid active basis, with about 35
mg and about 70 mg being only two examples of a unit
dosage:
For once-weekly dosing, an oral unit dosage
oy ote i a Lt 6
a —ime hesis. me of ‘weekly aa
dosages include a unit dosage which is useful for
osteoporosis prevention comprising about 35 mg of
the alendronate compound, and a unit dosage which
is useful for treating osteoporosis comprising about
70 mg of the alendronate compound.
'329 patent, col. 12, Il. 56-63 (emphasis added). In addition
to the above passage, at another point in the specification the
range for the normal unit dosage is further widened to “about
8.75 to about 140 mg.” '329 patent, col. 12, II. 52-55 (stating
that “a unit dosage typically comprises from about 8.75 mg
to about 140 mg of an alendronate compound on an
alendronic acid active weight basis”). The specification thus
suggests the patentee contemplated a range of dosages,
further compromising Merck's proposition that it acted as its
own lexicographer in defining “about” to mean “exactly.”
* We also note that Examples 7 and 8 in the '329 patent do not
contradict the construction we adopt on appeal because they are only
examples of the tablets that could be prepared according to the patent.
Neither example clearly states that the only embodiment of the claims
would be the exact formulations described therein.
15a
Finally, our construction of “about” eliminates the
problem pointed out by Teva that the district court's
construction of the term “about” renders other parts of the
claim superfluous. As Teva notes, the specification uses both
the term “about” and “on an alendronic acid basis” at least 15
times to describe a “dosage strength. If, as Merck urges,
“about 35 [or 70] mg” means exactly 35 (or 70) mg of
alendronic acid, then the oft-repeated phrase “on an
alendronic acid active basis” would be unnecessary since
so. Elekta, 214 F.3d at 1307 (construing claim to avoid
rendering the 30 degree claim limitation superfluous); Gen.
93 F.3d 766, 770
(Fed. Cir. 1996) (rejecting the district court's claim
construction because it rendered superfluous the claim
requirement for openings adjacent to the end walls). By
construing “about” to mean its accepted and ordinary
meaning of “approximately,” the phrase “alendronic acid
basis” is no longer excess verbiage, but is instead
because it is the noun that “about 35 [or 70] mg” modifies.
Because the patentee did not clearly redefine “about”
in the specification, and because the district court construed
the claim term in a manner inconsistent with the
specification, we reverse the district court's claim
construction. We thus hold that the term “about” should be
given its ordinary and accepted meaning of “approximately.”
C. —_ Invalidity
In light of the corrected claim construction we find
reversible error in the district court's obviousness analysis. A
patent claim is invalid “if the differences between the subject
matter sought to be patented and the prior art are such that
oo a————————————
l6a
the subject matter as a whole would have been obvious at the
time the invention was made to a person having ordinary
skill in the art to which said subject matter pertains.” 35
U.S.C. § 103(a) (2000). The ultimate issue of obviousness
turns on four factual determinations: (1) the scope and
content of the prior art, (2) the level of ordinary skill in the
art, (3) the differences between the claimed invention and the
prior art, and (4) objective indicia of nonobviousness.
Graham v. John Deere Co., 383 U.S. 1, 17-18 (1966). As
explained below, we find clear error in the trial court's
findings on these underlying facts.'® On reviewing these
factual bases, we conclude the district court also erred in
refusing to invalidate claims 23 and 37 for obviousness in
view of the 1996 Lunar News articles.
The central issue concerns the differences between
the aspects of the invention claimed at claims 23 and 37, and
the teachings of the Lunar News articles. As the district court
necessarily recognized, there are more similarities than
differences. These claims, and the July 1996 article, both
teach administering alendronate once a week instead of once
a day. These claims read in light of the specification, and the
July 1996 article, both indicate - and it has been conceded as
known in the art at the time'’ - that for treating or preventing
o-teoporosis a once-weekly dosage at seven times the daily
dose would be as effective as seven daily doses. The '329
patent, and both the April and July 1996 articles, explain the
motivation for a once-weekly dose as increasing patieni
compliance, by making it easier to take the drug (and incur
'° It makes no difference to this conclusion whether the court begins
with the claim construction set forth by the panel or the dissent. In either
case, the district court erred in finding the ‘329 patent was not invalid as
obvious in view of the Lunar News articles.
'' See Merck, 288 F. Supp. 2d at 624.
17a
the inconvenience of the rigorous dosing regimen less
frequently). Although the claims teach 70 or 35 mg doses
rather than the 80 or 40 mg doses disclosed in the July 1996
article, Dr. Arthur C. Santora - one of the co-inventors on the
'329 patent - admitted against Merck's interest that a once-
weekly 40 mg dose wouid be as effective as seven daily 5 mg
doses, and a once-weekly 80 mg dose would be as effective
as seven daily 10 mg doses, in preventing or treating
osteoporosis. There was no great leap required of those
skilled in the art to go from 40 or 80 mg once a week, the
pills available at the time to treat patients with Paget's
disease, to a 35 or 70 mg pill once a week. The district court's
conclusion that the claims are not obvious cannot rest on any
of these similarities between the claimed invention and the
two Lunar News articles.
The district court distinguished the two Lunar News
articles on grounds that they failed to explain how the once-
weekly dosing overcame concerns in the art with adverse Gl
side effects. Merck, 288 F. Supp. 2d at 628-29. We are left
with the firm conviction that this distinction is misplaced. As
noted, the district court found those in the art had identified
two types of adverse GI problems with alendronate. The first,
and most significant, involved esophageal injury or repetitive
irritation of the esophagus. The district court, reviewing the
October 1996 article by DeGroen in the New England
Journal_of Medicine, expressly recognized the literature
taught that complications related to alendronate were due to
“prolonged contact of the drug with the esophagus.” Merck,
288 F. Supp. 2d at 627. Confronted with this problem, Merck
revised its dosing instructions and sent the clarifying
materials io prescribing physicians in a March 1996 “Dear
Doctor” letter. After Merck sent this letter, the reported
incidence of GI distress fell to almost nothing even as the
number of patients being prescribed Fosamax doubled by
October 1996. Although the '329 patent focuses on this
18a
adverse GI side-effect, it provides no additional motivation to
overcome this problem beyond the motivation described in
the two articles. The ‘329 patent, both articles, and the
prevailing knowledge of those skilled in the art, recognized
that to the extent “dosing problems” were related to repetitive
irritation of the esophagus (from patients getting pills stuck
in their throats), taking fewer pills each week could reduce
the attending GI problems.’ Thus, the district court clearly
erred in finding any significant difference between the
claimed tavention and Ge two astictes os to Gus (ype oF Cl
problem.
The district court found a second adverse GI side-
effect related to the size of the dose, which Merck argued
gave rise to “the expectation by physicians in the field during
1996-1997 that alendronate sodium at doses over 20 mg
would not be well-tolerated in the prevention and treatment
of osteoporosis.” Merck, 288 F. Supp. 2d at 624; see also id.
at 622-23, 627-30 (discussing Chesnut study). Neither the
'329 patent nor the Lunar News articles explain how a higher
= As the 329 patent states:
[I}t is found that the admiistration of a biphosphonate at a high
relative dosage at a low relative dosing frequency causes less
adverse gastrointestinal effects, particularly esophageal effects,
compared to the administration of a low relative dosage at a
be especially beneficial in treating patients that have been
identified as suffering from or are susceptible to upper
gastromtestinal disorders, ¢.g.. gastrointestinal reflux disease
(i.e. “GERD"), esophagitis, dyspepsia (ic. heartburn), ulcers,
and other related disorders. In such. patients conventional
bisphosphonate therapy could potentially exacerbate or induce
329 patent, col. 3, 1. $7 - col. 4, I. 13 (emphasis added).
19a
once-weekly dosing regimen would avoid this set of dose-
related adverse side effects. The ‘329 patent sets forth no
human clinical or laboratory data showing the safety and
tolerability of the treatment methods claimed by the patent.
The only data provided in the '329 patent was generated in
beagles, an experiment discredited at trial and disregarded by
the district court in its decision. So while the district court
may be correct in finding the Lunar News articles may have
invited skepticism based on concerns for dose-related Gl
problems, the claimed invention adds nothing beyond the
teachings of those articles. Thus, the district court clearly
erred in finding any difference between the claimed invention
and the articles on this point.
The district court's only remaining distinction
between the claimed invention and the two Lunar News
articles goes to the probative value of the articles. The trial
court wrote that it “[was] not persuaded that the two Lunar
News articles, not published in peer-reviewed journals or
. authored by one skilled in the art, either alone or in
combination, overcame the serious side effect concerns
associated with higher dosage units of alendronate sodium.”
Merck, 288 F. Supp. 2d at 629. Although these indicia of
reliability - whether a study is peer-reviewed, and the
credentials of the author - properly go to weight when the
trial court has not excluded evidence as unreliable and
irrelevant, the district court's reliance on these factors to
20a
discounts the probative value of the two articles based on the
credentials of the author calls for closer scrutiny and casts
doubt on the findings that depend on this reasoning.
In short. the district court clearly erred in
distinguishing the claimed invention from the two Lunar
News articles offered as section 103 prior art. Contrary to the
district court's findings, these articles support the conclusion
that Merck's claims 23 and 37 are invalid as obvious.
For similar reasons we find the district court's
characterization of the scope and content of the prior art
favors invalidating claims 23 and 37 as obvious. The district
court described its larger task as identifying “a showing of
the teaching or motivation to combine prior art references.”
Merck. 288 F. Supp. 2d at 625 (quoting In re Gartside, 203
F.3d 1305, 1319 (Fed. Cir. 2000)). But as shown above, in
this case the Lunar News articles contain the relevant
teaching of the weekly dosing claimed in the '329 patent. The
“specific combination” of elements in claims 23 and 37
differs from the disclosure in the Lunar News articles only in
terms of a minor difference in the dosage; without this
difference, the Lunar News articles would anticipate claims
23 and 37 under section 102. For the Lunar News articles to
render claims 23 and 37 obvious, the district court need only
have found a suggestion or motivation to modify the dosages
from those in the articles to those in the claims. See, ¢.g.,
Sibia Neurosciences, Inc. v. Cadus Pharm. Corp., 225 F.3d
1349, 1356 (Fed. Cir. 2000). But as noted above, Merck's
own inventors admit the difference in dosing amount is
obvious. If anything, concern over dosing amount suggests
lowering the weekly dosage - from 80 to 70 mg, and from 40
to 35 mg, just as Merck did. The district court thus clearly
erred to the extent it found lacking any motivation to
combine existing knowledge with the Lunar News articles to
reach the claimed invention.
2la
The district court failed to ascertain the required
motivation to combine references to achieve the claimed
invention, and it ignored the plain teachings of the Lunar
News articles. As the court stated, “the issue is when viewing
the mosaic of prior art, whether those of ordinary skill in the
art would have had the motivation to formulate a once-
weekly seven-fold daily dose of alendronate, despite safety
concerns.” Merck, 288 F. Supp. 2d at 626.
The Lunar News articles had clearly suggested the
once-weekly dosing. They did so, as noted above, and as
described in the '329 patent, to avoid or minimize problems
related to dosing frequency. And as shown above, the district
court itself found this particular set of problems were of
greatest concern in the art. Indeed, to the extent the district
court finds Merck's weekly-dosing idea non-obvious because
it went against prevailing wisdom, the court must still
explain why Merck and not Dr. Mazess should get credit for
the idea. Because Merck's idea added nothing to what came
before, the district court's answer comes down to nothing
more than the credentials of the authors. In this case that
difference is not enough to avoid invalidating the claims."
The district court answered its own question
incorrectly, because its analysis of the prior art fails to credit
its own distinction between the “safety concerns” from
dosing frequency and dosing amount. As noted above, the
claimed invention does not address the problems with the
dosing amount, but only the more widespread problems of
we Although the court is unsure whether an obviousness ruling can ever
turn solely on the credentials of the inventors and prior art authors, where
the prior art has been admitted, it need not decide that question here. As
noted below, by the district court's own functional definition (if not its
actual finding) Dr. Mazess was one of skill in the art, and the Lunar News
was widely circulated in the field.
22a
the dosing frequency. The court's review of the scope and
content of the prior art itself focuses on this concern with
“prolonged contact of the drug with the esophagus.” Merck,
288 F. Supp. 2d at 627. This understanding of the prior art
does not support a conclusion that the claimed invention as a
whole was non-obvious in view of the prior art. See Para-
Ordnance Mfg. v. SGS Imports Int'l Inc., 73 F.3d 1085, 1087;
In re Kaslow, 707 F.2d 1366, 1374 (Fed. Cir. 1983). Insofar
as the district court relied on safety concerns related to
dosing frequency, the prior art favors the conclusion that
taking pills once a week was obvious.
Thus, the scope and content of the prior art confirms
that the invention claimed in claims 23 and 37 would have
been obvious in view of the Lunar News articles. To the
extent the district court interpreted the scope of the prior art
otherwise, that was clear error.
We likewise find clear error in the district court's
conclusion that Dr. Mazess was not skilled in the relevant art.
The district court failed to credit the evidence showing
Mazess's Lunar News was widely distributed among those
working in the field of osteoporosis. Moreover, while we
recognize the importance academic or professional training
plays in establishing expert quaiifications or the probative
value of a section 103 reference, we think the district court
failed to give proper crecit to the fact that Dr. Mazess was an
expert in osteoporosis. In focusing on Dr. Mazess's academic
training, the district court ignored its own finding that one of
skill in the art would be someone “working in the field of, or
doing research on, osteoporosis.” Thus, the district court
erred in dismissing or minimizing the probative value of the
Lunar News articles.
Finally, the district court erred ir its weighing of
secondary considerations of non-obviousness. Although the
23a
district court correctly found Merck's once-weekly dosing of
Fosamax was commercially successful, in this context that
fact has minimal probative value on the issue of obviousness.
Merck, 288 F. Supp. 2d at 629-30. Commercial success is
relevant because the law presumes an idea would
successfully have been brought to market sooner, in response
to market forces, had the idea been obvious to persons skilled
in the art. Thus, the law deems evidence of (1) commercial
success, and (2) some causal reiation or “nexus” between an
invention and commercial success of a product embodying
that invention, probative of whether an invention was non-
obvious. See Graham, 383 U.S. at 17-18 (“Such secondary
considerations as commercial success, long felt but unsolved
needs, failure of others, etc., might be utilized to give light to
the circumstances surrounding the origin of the subject
ee a ae cae hee Ge
these inquiries may have relevancy.”);
bicNeil-PPC. Inc. v. L. Perigo Co. 337 F.3d 1362, 1370
(Fed. Cir. 2003).
That rationale has no force in this case. In Graham the
Supreme Court relied on the reasoning from a law review
note discussing commercial success. See Graham, 383 U.S.
at 17-18, citing Note, Subtests of Nonobviousness”: A
Nontechnical Approach to Patent Validity. 112 U. Pa. L. Rev.
1169, 1175 (1964). The article suggested “[t}he possibility of
market success attendant upon the solution of an existing
problem may induce innovators to attempt a solution. If in
fact a product attains a high degree of commercial success,
there is a basis for inferring that such attempts have been
made and have failed.” As our predecessor court explained in
In re Fielder, 471 F.2d 640, 644 (C.C.P.A. 1973), “[t}hese
rationales, presumably approved by the [Supreme] Court, tie
commercial success and the like directly to the practical,
financial source of impetus for research and development.”
But that chain of inferences fails on these facts. Although
24a
commercial success might generally support a conclusion
that Merck's claimed invention was non-obvious in relation
to what came before in the marketplace, the question at bar is
narrower. It is whether the claimed invention is non-obvious
in relation to the ideas set forth in the Lunar News articles.
Financial suceess is not significantly probative of that
question in this case because others were legally barred from
commercially testing the Lunar News ideas. Dr. Mazess, for
example. could not put his ideas to practice in 1996 - he
could only exhort Merck to try it. They did.
In this case Merck had a right to exclude others from
practicing the weekly-dosing of alendronate specified in
claims 23 and 37, given (1) another patent covering the
administration of alendronate sodium to treat osteoporosis,
U.S. Pat. No. 4,621,077 (issued Nov. 4, 1986); and (2) its
exclusive statutory right, in conjunction with FDA marketing
approvals, to offer Fosamax at any dosage for the next five
vears. 2’ U.S.C. § 355(cK3\D\ii) (2000). Because market
entry by others was precluded on those bases, the inference
of non-obviousness of weekly-dosing, from evidence of
commercial success, is weak. Although commercial success
may have probative value for finding non-obviousness of
Merck's weekly-dosing regimen in some context, it is not
enough to show the claims at bar are patentably distinct from
the weekly-dosing ideas in the Lunar News articles. Thus, we
conclude the district court misjudged this factor as
confirming its conclusion of non-obviousness.
In short, we find the relevant Graham factors
establish claims 23 and 37 of the ‘329 patent are obvious in
view of the April 1996 and July 1996 Lunar News articles.
Thus, we reverse the district court and hold claims 23 and 37
invalid.
If. CONCLUSION
We reverse the district court's claim construction and
hold that “about” should be construed consistently with its
ordinary meaning of “approximately.” In addition, we vacate
the district court's determination that the '329 patent was not
invalid as obvious. We hold claims 23 and 37 invalid as
obvious and not infringed. The district court's judgment of
infringement is therefore
REVERSED
COSTS
26a
United States Court of Appeals for the Federal Circuit
04-1005
MERCK & CO., INC..,
Plaintiff-Appellee.
v.
TEVA PHARMACEUTICALS USA, INC.,
Defendant-Appellant.
RADER. Circuit Judge. dissenting.
This case shows the consequences of paying only lip
service to the often-cited, but rarely-followed lexicographer
rule and the basic jurisprudential principle of according trial
courts proper deference.
Elect the Lexicographer Option at Your Own Risk
With this court's claim constructions wavering
between the plain meaning rule (often a subtle way for judges
to umpose their own semantic subjectivity on claim terms,
sec. eg. K-2 v. Salomon. 191 F.3d 1356 (Fed. Cir. 1999)
“permanent” affixation of the wheels to the skate boot in the
context of in-line skates did not include a bolt that could only
be reached by tearing apart the shoe)) and the “specification
Ober alles” rule (often a way for judges to import limitations
na included in the claim, see, ¢.g., Phillips v. AWH Corp.,
363 F.3d 1207, 1213-14 (Fed. Cir. 2004), vacated, reh'g en
bam granted. 376 F.3d 1382 (Fed. Cir. July 21, 2004)), a
patent applicant might suppose that the best option to define
the scope of the claim language might be the lexicographer
rule. Under the lexicographer rule, an inventor acts as an
27a
independent lexicographer and can even give claim terms a
— “inconsistent with its — henge
Corp.. 320 F.3d 1339, 1347 (Fed. Cir. 2003) (citing Teleflex.
Inc. v. Ficosa N. Am. Corp., 299 F.3d 1313, 1325-26 (Fed.
Cir. 2002)); see also Teleflex, 299 F.3d at 1325 ("[A]n
inventor may choose to be his own lexicographer if he
defines the specific terms used to describe the invention ‘with
reasonable clarity, deliberateness, and precision.” (quoting In
re Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994))). Indeed,
this court often acknowledges that an applicant, acting as a
lexicographer, may define "black" as “white.” See Hormone
, 904 F.2d 1558,
1563 (Fed. Cir. 1990) ("It is a well-established axiom in
patent law that a patentee is free to be his or her own
lexicographer and thus may use terms in a manner contrary to
or inconsistent with one or more of their ordinary
meanings."); see also, ¢.g., Int'l Rectifier Corp. v. IXYS
Corp., 361 F.3d 1363, 1373 (Fed. Cir. 2004) (patentee
defining “annular,” which ordinarily means in the shape of a
ring, to describe structures that are not circular or curved, but
polygonal). In this case, the patentee used the lexicographer
rule to define a lengthy phrase. In its definition, the patentee
defined the phrase with precise values. The patentee’s
definition, however, fell five letters short of success because
the phrase included the word “about.” This court seized on
that word, gave it an ordinary meaning, and cast aside the
lexicographer rule without a convincing explanation.
Moreover, this court overturned the result of a lengthy
district court trial for the sole reason that the trial court
applied this court's lexicographer rule. | find it hard to
explain to the district court how it erred by following this
court's rules.
The disputed term in claim 23 of the '329 patent is the
phrase “about 70 mg of alendronate monosodium trihydrate.
28a
on an alendronic acid basis.” Similarly, the disputed term in
claim 37 is the phrase "about 35 mg of alendronate
monosodium trihydrate, on an alendronic acid basis." Teva
contends that this court should parse out one word in that
phrase, “about,” and accord that single word its ordinary
meaning of “approximately.” Merck, on the other hand,
contends that the term "about" is inseparable from the entire
phrase, which it defines under the lexicographer rule to
account for the variability in the active ingredient weight that
would result from the use of a salt of alendronic acid.
The specification shows the proper interpretation of
the disputed phrase. See Vitroni j
Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996) ("The specification
acts as a dictionary when it expressly defines terms used in
the claims or when it defines terms by implication."). In the
specification of the '329 patent, the patentee exercised the
lexicographer option and defined the disputed phrase as
follows:
Because of the mixed nomenclature currently in use
by those o[f] ordinary skill in the art, reference to a
specific weight or percentage of a bisphosphonate
compound in the present invention is on an acid
active weight basis, unless otherwise indicated
herein. For example, the phrase "about 70 mg of a
bone resorption inhibiting bisphosphonate selected
from the group consisting of alendronate,
pharmaceutically acceptable salts thereof, and
mixtures thereof, on an alendronic acid active
weight basis" means that the amount of the
bisphosphonate compound selected is calculated
based on 70 mg of alendronic acid.
'329 patent, col. 10, 1. 65 - col. 11, 1. 8.
29a
In a passage that classically invokes this court's
lexicographer doctrine, the patentee clearly, deliberately, and
precisely defined the phrase “about 70 mg of a bone
consisting of alendronate, pharmaceutically acceptable salts
thereof, and mixtures thereof, on an alendronic acid active
weight basis.” The patentee set forth that entire term with
70 mg of alendronic acid.” '329 patent, col. 11, Il. 2 - 8
(emphases added). The choice of the words “phrase” and
Medzam Lid., 133 F.3d 1473, 1477 (Fed. Cir. 1998).
To underscore the choice to define the phrase
|
A
7
the art.” i eee ok 10, Il. 65-66. Therefore,
casual reader, let alone one with skill in this art,
immediately recognize that the patentee intended to
Mth
HE
uf
a
{Ht
art notice of the change.” (quoting [ntellicall, Inc. v.
Phonometrics, Inc., 952 F.2d 1384, 1388 (Fed. Cir. 1992))).
30a
the language of this definition explains further the
scientific reason that an express definition is necessary.
Alendronate monosodium tnhydrate is a bisphosphonate
selected from the group consisting of alendronic acid,
pharmaceutically acceptable salts thereof. and mixtures
thereof. A salt or a mixture may require a different weight to
achieve the same number of bisphosphonate molecules
present in 70 mg of alendronate.
The patentee did not leave this difference vague.
however, but instructed that the precise dose in claim 23 -
“about 70 mg of alendronate monosodium trihydrate, on an
alendronic acid basis” - means that the amount of alendronate
monosodium tnhydrate is calculated based on 70 mg of
alendronic acid. Similarly. the disputed language of claim 37
~ “about 35 mg of alendronate monosodium trihydrate, on an
alendronic acid basis” - means that the amount of alendronate
monosadium tihvdrate is calculated based on 35 mg of
alendronic acid. The word “about” in the definéd phrase takes
imo account the variability of the weight of the active
ingrediemt that would result from using different salts of
alendronic acid in the tablets. instead of the acid itself. In
other words. a heavier salt would require more by weight to
acheeve the same number of alendronate molecules. For
exampic. about 70 mg of alendronate sodium, on an
alendronic acid active basis. contains the same number of
molecules of alendronate as 70 mg of alendronic acid,
regardless of the actual weight of the alendronate sodium in
the tablet
Wh respect to the word “about.” the patentee
mcluded that word in the entire phrase expressly defined in
the specification and set off by quotation marks. Therefore,
Tes court cannot. without disturbing the patentee's express
aefeunon of the entire phrase, abstract that term out of its
woenex: and supply an ordinary meaning Thus, by abstracting
3la
"about" out of the patenice’s express definition, this court's
opinion defeats the patentee's choice of words, punctuation,
and phrascology and instead extracts a single word from its
context in the phrase. Accordingly, the majority rewrites the
express definition cither by moving the word “about” outside
of the quotation marks of the defined phrase or by inserting
the word “about” into the definitional portion of the sentence
so that it would read “the amount of the bi
compound is calculated based on about 70 mg of alendronic
acid.” If the patentee had chosen either of those two
phraseologies, the majority opinion might be correct in its
analysis. But because the patentee did not, this court cannot
give any principled reason that the district court erred in
applying the lexicographer rule. Contrary to this court's rules,
language not chosen by the patentee. See, ¢.¢., Chef Am.,
. 358 F.3d 1371, 1374 (Fed. Cir
2004) (repeating the well-established rule that “courts may
not redraft claims”).
to the disputed phrases in claims 23 and 37 consistent with
the specified lexicography, thus completely dispelling any
notion of ambiguity in the term “about.” In particular,
Examples 7 and 8 corroborate the express definition.
Example 7 states that “[t]ablets containing about 35 mg of
alendronate, on an alendronic acid active basis, are prepared
using the following weights of ingredients” and lists
alendronate monosodium trihydrate requiring a mass of 45.68
mg. See '329 patent, col. 19, II. 14 - 21. Similarly, example 8
states that "[a} liquid formulation containing about 70 mg of
alendronate monosodium trihydrate, on an alendronic acid
active basis, per about 75 mL of liquid is prepared using the
following weights of ingredients” and lists alendronate
monosodium trihydrate having a mass of 91.35 mg. Id. at col.
19, Il. 44 - $2. In these examples, the applicant supplied an
32a
exact weight that equates with “about 70 mg of alendronate
...on an alendronic acid active basis.” Accordingly, the
district court did not err in construing “the disputed claim
terms ‘about 70/35 mg’ to mean the equivalent of 70/35 mg of
alendronic acid when taking into account molecular weight
variances for its derivatives that carry accessories.” Merck.
288 F. Supp. 2d at 616. The district court followed this
court's rules.
Deference to Trial Courts:
Time for “Truth in Advertising?”
This is the classic “close case,” so close in fact that
ultimately two federal judges (one of whom conducted an
entire bench trial on this issue) and the United States Patent
and Trademark Office agreed with Merck & Co., and two
federal judges agreed with Teva Pharmaceuticals. The
United States District Court of Delaware tried this case from
March 4 - 7, 2003, then issued a 75-page opinion analyzing
the claims and arguments in consummate and accurate detail.
Merck & Co. v. Teva Pharms. USA, Inc., 288 F. Supp. 2d 601
(D. Del. 2003). This court received the typical briefs from the
parties, an appendix containing selected portions of the
record, and heard a total of approximately thirty minutes of
argument by the parties on the issues before this court.
Despite the distnct court's superior tools and time to evaluate
the complete record, to hear and inquire from expert and fact
witnesses, to delve into countless related details, to probe the
scientific and semantic context, and to entertain argument as
long as necessary for clarity, this court with its reading three
briefs before its half-hour hearing becomes enamored with its
own analysis of a very close issue and reverses the district
court.
This court often hears criticism from district court
judges that its reversal rate on claim construction issues far
33a
The Law. Technology ind the Future ofthe Fed Symposium,
Se et Oe 671 (2003)
(Symposium |) (district judges discussing problems with this
court's high reversal rate on claim construction issues), see
Gregory J. Wallace, Note, Toward Certainty and Uniformity
in Patent Infringement Cases after Festo and Markman: A
Proposal for a Specialized Patent Trial Court with a Rule of
Greater Deference, 77 S. Cal. L. Rev. 1383, 1391 (2004 )
(discussing various studies regarding this court's reversal rate
on claim construction issues). In response, nearly every judge
on this court has publicly professed to accord some level of
deference to district courts regardless of this court's de novo
review of claim construction issues. See, ¢.g., Symposium |
at 680 (a district court judge stating “I have certainly heard a
number of federal circuit judges agree, that the CAFC gives
some deference to a well-reasoned opinion, as a practical
a rnpotae. 1s Et CS 08 SS. St
m Nerigstionsl Aide, 54 Case W. Res L’ Rew 757, 76)
(2004) judge of the Federal Ciscuit stating: “Review is really
not de novo after all. It is unfortunate that there is no label in
between de novo and clear error review. Functionally, claim
construction falls in this middle ground."). Either the Federal
Circuit accords deference in accordance with its public
protestations or it does not in accordance with its legal
standard barring any deference. If the former, this court has a
“truth in advertising” problem. Its actual practice clashes
with its professed legal duty. If the latter, this court has a
different kind of “truth in advertising” problem.
In this case, this court eschews all deference. a
particularly striking choice in the face of a very close case
and a district court whose diligent and intelligent process and
resolution earned more respect than it received. | am not
APPENDIX B
United States Court of Appeals for the Federal Circuit
04-1005
MERCK & CO., INC.,
Plaintiff-Appeliee,
v.
TEVA PHARMACEUTICALS USA, INC.,
Defendant-Appellant.
ON PETITION FOR PANEL REHEARING AND
REHEARING EN BANC
Before MICHEL, Chief Judge, NEWMAN, MAYER,
LOURIE, CLEVENGER, RADER, BRYSON, GAJARSA,
LINN, DYK, and PROST, Circuit Judges:
ORDER
A combined petition for panel rehearing and
rehearing en banc was filed by the Appellee, and a response
thereto was invited by the court and filed by the Appellant.’
' An amicus curiae brief was filed by the Pharmaceutical
Research and Manufacturers of America.
Se a
36a
The petition for reliearing was referred first to the merits
panel that heard the appeal. Thereafter, the petition for
rehearing en banc, response, and the amicus curiae brief were
referred to the circuit judges who are authorized to request a
poll whether to rehear the appeal en banc. A poll was
requested, taken, and faiied.
Upon consideration thereof,
IT IS ORDERED THAT: ©
(1) The petition for pane! rehearing is denied.
(2) The petition for rehearing en banc is denied.
(3) The mandate of the court will issue on April 28,
2005.
NEWMAN and LOURIE, Circuit Judges, would
rehear the appeal en banc.
LOURIE, Circuit Judge, with whom MICHEL, Chief
Judge, and NEWMAN, Circuit Judge, join, dissents in a
separate opinion.
SCHALL, Circuit Judge, did not participate in the
vote.
FOR THE COURT
APR 21 2005.
Date Jan Horbaly
Clerk
ce: John F. Lynch, Esq.
James Galbraith, Esq.
William F. Lee, Esq.
FILED
U.S. COURT OF APPEALS FOR
THE FEDERAL CIRCUIT
Apr 21, 2005
JAN HORBALY
CLERK
Wa
United States Court of Appeals for the Federal Circuit
04-1005
MERCK & CO. INC.,
Plaintiff-Appellee,
‘.
TEVA PHARMACEUTICALS USA, INC.,
Defendant-Appellant.
LOURIE. Circuit Judge. with whom MICHEL, Chief Judge,
ant NEWMAN, Circuit Judge. join. dissenting from order
denying rehearing en hanc.
| respectfully dissent from the court's declining to
bear thes case en banc. In my opinion. the panel erroneously
comchudes that commercial success is not probative because
“others were legally barred” from commercially testing
oomtmm sdezs m the poor art Moreover. | believe the panel
ered 2 imiomg commercial success to the failure of others.
Commercial success is a fact question. and. once it is
csu>inshed. 2s found here by the trial court. the only other
guesocn 1s whether the success is attributable to the claimed
mvempon “nexus”) rather than to other factors such as
maxis power. advernsing. demand for al) products of a given
[pe 2 msm ecomomy that “lifts al] boats.” etc. It is not
“eaves > 6a «6Cmabiimy oof others tw test various
iormuiamons Decause of the existerme of another patent.
Success 1s success. The panels rule is especially unsound in
te comer of @ mprovemem patent as here, because it
39a
holds in effect that commercial success for an improvement
is irrelevant when a prior patent dominates the basic
invention.
Commercial success is also independent of any
"failure of others," as that is another, separate secondary
consideration.
Respectfully, the full court should have reheard the
appeal to eliminate the confusion in the law that the panel
opinion creates.
40a
APPENDIX C FILED
Sep 24 943 AM ‘3
CLERK US. DISTRICT CO
DISTRICT OF DELAWARE
IN THE UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF DELAWARE
MERCK & CO., INC.,
Plaintiff, C.A. No. 01-0048 (JJ?
(CONSOLIDATED)
Vv.
TEVA PHARMACEUTICALS USA, INC.,
Defendant.
=
FINAL JUDGEMENT ORDER
PURSUANT TO FED. R. CIV. P. 54(b)
For the reasons set forth in this Court's Memorandum
Opinion of August 28, 2003,
IT IS HEREBY ORDERED that:
l. Claims 23 and 37 of US. Patent No. 5,994,329
(“the '329 Patent”) are not invalid;
2. The '329 Patent is not unenforceable;
3. Pursuant to 35 U.S.C. § 271(e)(4)A), the
effective date of any Food and Drug Administration approval
of Defendant's Abbreviated New Drug Application No. 75-
710 with respect to tablets containing 76 mg or 35 mg of
alendronate sodium (on an alendronic acid basis) for
Prer AUAN ADIT PDVa
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treatment or prevention of osteoporosis, respectively, will be
a date not earlier than July 17, 2018, the expiration date of
the "329 Patent;
4. Pursuant to 35 U.S.C. § 271(e)4)\B),
Defendant, its officers, agents, attorneys and employees, and
those persons in active concert or participation with any of
them who receive actual notice of this Order by personal
service or otherwise, are hereby enjoined from engaging in
the commercial use, offer to sell, or sale within the United
States, or importation into the United States, of tablets
containing 70 mg or 35 mg of alendronate sodium (on an
alendronic acid basis) for the treatment or prevention of
osteoporosis, respectively, on or before July 17, 2018, the
expiration date of the '329 Patent;
5. Judgment is entered in favor of Plaintiff and
against Defendant on Plaintiff's claims of infringement of
claims 23 and 37 of the '329 Patent and on Defendant's
defenses to those ciaims, and in favor of Plaintiff and against
Defendant on Defendant's counterclaim relatirig to the
unenforceability of the '329 Patent; and
6. On December 2, 2002, the Court entered a
Final Judgment Order in Consolidated Actions C.A. No. 00-
035-JJF and C.A. No. 00-052-JJF regarding U.S. Patent No.
4,621,077 (the “077 patent”). The Court entered Judgment
that Teva's filing of its Abbreviated New Drug Application
No. 75-710 infringed claim 1 of the '077 patent, that the '077
patent is not invalid, and that the patent term extension of the
‘077 patent is valid. Teva appealed the Court's Final
Judgment Order to the United States Court of Appeals for the
Federal Circuit, and the appeal is pending. Per the parties’
agreement, and Court's Order of March 7, 2003, the outcome
of the appeai (and any subsequent proceedings) will be
_ dispositive of all issues regarding Merck's infringement
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claims and Teva's counterclaims brought in this action
regarding the '077 patent.
Accordingly, in accordance with Fed. R. Civ. P. 54(b),
there is no just reason for delay in entering this Judgment and
the Court directs that it be entered.
SO ORDERED this 23 day of September, 2003.
United States District Judge
43a FILED
CLERK US DISTRICT COURT
DISTRICT OF DELAWARE
APPENDIX D 2003 AUG 28 PM 2:42
IN THE UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF DELAWARE
MERCK & CO., INC.,
Plaintiff,
v. Civil Action No. 01-048 (JJ
(Consolidated)
NICHOLS, ARSHT & Wi
Of Counsel: John F. Lynch, Nicolas G and
Stephen FE. Edwards, Esquires of HOWREY SIMON
ARNOLD & WHITE, LLP, Houston, Texas.
Paul D. Matukaitis, Edward W. Murray, and Gerald M
Devlin, Jr. Esquires of MERCK & CO., Whitehouse Station
New Jersey.
Attorneys for the Plaintiff
Josy W. Ingersoll, and Adam W. Poff Esquires of YOUNG
CONAWAY STARGATT & TAYLOR, LLP, Wilmington,
Delaware.
Of Counsel: James Galbraith, Maria Luisa Palmese and
William G James, Il, Esquires of KENYON & KENYON,
New York, New York.
Attomeys for Defendant Teva Pharmaceuticals, USA. Inc.
Farnan, District Judge.
L. Procedural Background
Plaintiff, Merck & Co., Inc. (“Merck”) is a Delaware
corporation with its principal place of business in New
Jersey. Defendant, Teva Pharmaceuticals USA, Inc. (“Teva”)
is a Delaware corporation with its principal place of business
in Pennsylvania. Merck is the owner of the entire right, title
and interest in United States Patent No. 5,994,329, entitled
“Method for Inhibiting Bone Resorption” (the “"329 Patent”),
which issued November 30, 1999, naming as inventors
Anastasia G Daifotis, Arthur C. Santora I, and John Yates.
Merck filed the application for the '329 Patent on July 22,
1997. The "329 Patent is set to expire on August 14, 2018.
(PTX 1).
Merck listed the ‘329 Patent in the Federal Drug
Administration's (“FDA”) publication “Approved Drug
Products with Therapeutic Equivalence Evaluations” (the
“Orange Book”) in connection with its 70 mg and 35 mg
dosage for alendronate sodium, which Merck markets under
the name “Fosamax.” On October 3, 2000, Teva filed a
supplement to existing Abbreviated New Drug
Application (“ANDA™) seeking FDA approval to market
generic versions of Merck's 70 mg aiendronate sodium
product for weekly administraiion. Included with Teva's
ANDA filing were “paragraph IV” certifications (21 U.S.C. §
355 (j) (2) (A) (vii) (TV)) asserting that the Patents listed in
the Orange Book, including the '329 Patent, are invalid,
unenforceable or would not be infringed by the commercial
marketing of Teva's proposed product. Merck filed this action
on January 21, 2001, alleging that Teva's filing of its
supplement was an act of infringement under 35 U.S.C. §
271 (e) (2) (A). Thereafter, Merck listed U.S. Patent No.
6,225,294 (the ““294 Patent”) in the Orange book and Teva
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filed a paragraph IV certification asserting that the ‘294
Patent is invalid, unenforceable or would not be infringed by
the commercial marketing of Teva's proposed 70 mg
alendronate sodium product. On October 4, 2001, Merck
filed Civil Action No. 01-675-JJF, alleging that Teva's filing
of its supplemental ANDA was an act of infringement of the
‘294 Patent under 35 U.S.C. § 271 (e) (2) (A).
Subsequently, Teva filed another supplement to its
ANDA, seeking approval to market a generic version of
Merck's 35 mg Fosamax product. The supplement also
included a paragraph IV certification asserting that all the
listed patents were invalid, unenforceable or would not be
infringed by Teva's commercial marketing of its proposed
product. On November 6, 2001, Merck filed Civil Action No.
01-728, alleging that the filing of Teva's supplement to the
ANDA was an act of infringement under 35 U.S.C. § 271 (e)
(2) (A). On January 14, 2002, the Court consolidated all three
cases under Civil Action No. 01-048.
One of the listed patents against which Teva certified
was U.S. Patent No. 4,621,077 (“the '07/ Patent”), which had
already been the subject of litigation between the parties in
this Court (Civil Action No. 00-035-JJF) in connection with
Teva's application to market alendronate sodium for daily
administration. The Court entered judgment in favor of
Merck in that case on December 2, 2002, and an appeal from
that judgment is now pending in the United States Court of
Appeals for the Federal Circuit. (D.I. 123-1). The parties
agreed that they will be bound in this case, with regard to
issues concerning the '077 Patent, by a final decision in the
prior litigation. (D.I. 128). Prior to trial Merck stipulated that
the only claims at issue in this litigation are claims 23 and 37
of the '329 Patent and further stipulated that it would not
allege an invention date for those claims prior to July 22,
1997. (D.1. 128).
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Teva stipulated that if found valid and enforceable,
claims 23 and 37 of the "329 Patent would be infringed by the
commercial marketing of Teva's proposed 70 mg and 35 mg
alendronate sodium products for weekly administration. (D.1.
109, Pretrial Order, Tab 1, $f 8-9). The issues of validity and
enforceability of the "329 Patent were tried before the Court
from March 4-7, 2003.
The Court has jurisdiction over the parties and the
subject matter pursuant to 28 U.S.C. § 1338 (a). Additionally,
venue is appropriate under 28.U.S.C. § 1391(c) and §
1400(b). Neither jurisdiction nor venue are contested by the
parties. This Opinion constitutes the Court's Findings of Fact
and Conclusions of Law with respect to the issues tried
before the Court.
Il. The '329 Patent and Bone Biology In General
The '329 Patent discloses less-frequent-than daily
administration of bisphosphonates (¢.g., alendronate) to
inhibit bone resorption. (D.1. 143 at 8). Claims 23 and 37, the
only asserted claims, relate specifically to the treatment and
prevention of osteoporosis by once-weekly administration of
alendronate. Osteoporosis is related to processes that are
imbalanced in bone, and therefore, the Court will discuss the
background of bone biology as it relates to osteoporosis and
the use of alendronate for treatment of the disease.
Bone is the tissue that provides mechanical support to
the body. It is made up of a protein matrix, which is overlaid
with mineral to give it hardness. (Russell' at 108-109; DTX
523 at 2). Two principal types of cells maintain bone: 1)
osteoclasts, which break down bone, and 2) osteoblasts,
' The bench trial transcript is cited throughout the Opinion by a
notation to the witness and the page number of the transcript.
them, leaving defects in the bone structure. The destruction
words, bone is destroyed and built at the same rate. (Russell
at 109-110; DTX 523 at 3-4).
In osteoporosis, bone destruction and formation are
no longer balanced and bone is destroyed faster than it is
replaced. Therefore, osteoporosis can lead to bone that is
thinner, weaker, more fragile and porous. (Russell at 110-
115; DTX 523 at 7, 8). Osteoporosis is treated primarily by
inhibiting bone resorption - thus restoring the balance
between bone destruction and formation. Alendronate
inhibits bone resorption by blocking the bone destroying
effects of osteoclasts. (Russell at 116-117). A small portion of
the ingested drug makes its way to and adheres to the bone
surface, where it resides until it is taken up by osteoclasts.
bone. (Russell at 121-122; DTX 523 at 10).
Paget's disease is also 2 common bone disease
characterized by increased bone resorption. Jn Paget's
disease, increased bone remodeling occurs in localized areas
of the skeleton. If Paget's disease is not detected and treated
early it can lead to an increase in bone size, fractures, and
deformity. (Russell at 97). Like osteoporosis, Paget's disease
is treated by inhibiting bone resorption with alendronate.
(Russell at 125-126).
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Ill. Teva's Motion in Limine to Preclude Merck From
Relitigating the Factual Findings Undertying the
Decision in Teva Pharmaceuticals Ltd. et al. v.
Instituto Gentili Spa et al. (D.1. 113).
Teva filed a Motion in Limine te Preclude Merck
from Relitigating the Factual Findings Underlying the
Decision in Teva Pharmaceuticals Lid et al. Istituto Gentili
Spa et al., (High Court of Justice, Chancery Division, Patents
Court, January 21, 2003)). (D.1. 113). Accordingly, the Court
will discuss the motion in limine before it delves into the
~~tssues of validity and enforceability of the '329 Patent.
Teva's principal defense in this case is that claims 23
and 37 are invalid because the claimed invention is
anticipated or would have been obvious in view of the prior
art. At the same time that the parties were litigating the
validity of the ‘329 Patent in this Court, they were also
involved in a case in the British High Court of Justice (the
“High Court”). That case was a challenge by Teva and others
to the validity of the European Patent No. 998,292 (the “292
Patent”), which corresponds to the '329 Patent, and is based
on the same provisional applications filed in July 1997. Teva,
by its motion, contends that the ‘292 Patent covers the
identical concept as the ‘329 Patent: the once-weekly dosing
of alendronate sodium to treat osteoporosis, using seven
times the normal daily dose”
The High Court conducted a full trial on the merits
from November 5-8, 2002, and heard further arguments from
counsel on November 12-13, 2002. The trial involved live
testimony from Merck's expert Dr. Socrates Papapoulos, who
? This claim is in the form of a “Swiss claim.” Such claims are used in
attempts to avoid restrictions on claiming methods of treatment, which
are unpatentab‘e in many countries.
49a
is Merck's expert in this case. In addition, Merck offered the
testimony of Dr. Yates, the principal inventor of the '329
Patent, who also testified in this case. On January 22, 2003,
Justice Jacob of the High Court found that the claimed
invention was invalid because it would have been obvious to
a person skilled in the art, it claims a method of treatment,
and is incapable of industrial application.
A. Applicable Legal Principles
Teva contends that the Court should adopt the High
Court's factual findings concerning obviousness pursuant to
the doctrine of collateral estoppel. Collateral estoppel is
appropriate if: (1) the issue is identical to one decided in the
first action; (2) the issue was actually litigated in the first
action; (3) resolution of the issue was essential to a final
judgment in the first action; and (4) plaintiff had a full and
fair opportunity to litigate the issue in the first action. Micron
., 189 F. Supp. 2d 201, 209
(D. Del. 2002) (citations omitted). Additionally, the doctrine
of collateral estoppel applies in patent cases. See Blonder-
Foundation, 402 U.S. 313 (1971).
B. Parties’ Contentions
1. Teva's Contentions
By its motion, Teva contends that Merck had the
identical motivation in litigating the British case as it does in
the instant case: to discredit the Lunar News (a prior art
reference) and Teva’s reliance on its teachings. Moreover,
Teva contends that Merck's barristers were afforded a full
and fair opportunity to cross-examine all of Teva's witnesses
and did so at length. Teva contends that the evidence was
heard by Justice Jacob of the High Court, who is experienced
in patents.
50a
On January 22, 2003, Justice Jacob found the '292
Patent invalid and entered judgment against Merck. In its
motion, Teva concedes that the legal standard may vary
between Britain and the United States; nevertheless, Teva
contends that regardless of the differences, if any, between
the legal standards for determining validity, collateral
estoppel should still apply to the resolution of the underlying
factual issues. Specifically, Teva contends that all of the
elements of collateral estoppel are met in this case with
regard to the High Court's factual findings on obviousness.
First, Teva contends that collateral estoppel applies to
fact findings of foreign courts. Teva argues that courts have
recently recognized that parties who litigate in a foreign court
should be bound by the results of that litigation to the extent
that the requirements of the collateral estoppel doctrine are
met. For example, Teva points to Vas-Cath, Inc. v. Mahurkar,
745 F. Supp. 517 (N.D. Ill. 1990), rev'd on other grounds,
935 F.3d 1555 (Fed. Cir. 1991), where the parties extensively
litigated the issue of obviousness in Canada, and the district
court held that the parties were bound by the fact-finding of
the Canadian Court. Additionally, Teva points to Northlake
| _v. Glav ., 958 F. Supp.
373, 379 (N.D. Ill. 1997) (“Northlake I”) ‘and Northlake
Marketing & Supply, Inc. v. Glaverbel, S.A.. 986 F. Supp.
471, 475-76 (N.D. Ill. 1997) (“Northlake II”), where the
parties had previously litigated the validity of a Belgian
patent that corresponded to the United States patent in suit.
The district court in those cases held that the Belgian Court's
conclusions about the scope and content of prior art were
binding on the parties in the United States litigation.
Further, Teva directs the Court to Oneac Corp. v.
Raychem Corp., 20 F. Supp. 2d 1233, 1242-1243 (N.D. Ill.
1998), where a corresponding European patent was litigated
in the High Court and the district court held that with respect
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to the United States patent, it would not give preclusive effect
to questions of law or mixed questions of law and fact, but it
would adopt the British Court's factual findings. Additionally,
Teva points to Federal Circuit decisions that have declined to
afford collateral estoppel effects to judgments in foreign
cases, but distinguishes them on the basis that those decisions
were predicated on what the Federal Circuit views as
different standards of patentability in other countries. See,
e.g. itroni _v. Daig Corp., 789 F.2d 903 (Fed. Cir.
1996) (declining to adopt German tribunal's determination
that corresponding German patent was invalid in view of
different legal standards); In re Duhlberg, 472 F.2d 1394
(C.C.P.A. 1973) (same).
Second, Teva contends that the issues were the same
in the British litigation; the obviousness of administering
alendronate sodium once a week at a dose of about seven
times the daily dose. Further, Teva argues that the issue of the
scope and content of the prior art are the same in both cases;
whether the Lunar News publications taught the
administration of alendronate sodium once a week, and
whether the prior art taught that the dose should approximate
seven times the daily dose. In addition, Teva argves that
Merck's fear defense is an issue in both cases. Merck claims
that persons skilled in the art would have rejected the Lunar
News teachings because of the fear that patients would not
tolerate the larger dose. Merck raised the issue in Britain, and
after considering the evidence, the High Court concluded that
the “fear defense fails”. For example, the High Court found
that the rare instances of esophageal side effects were
attributed primarily to failure to follow the dosing
instructions (D.I. 114, Ex. A, q 65).
Third, Teva argues that the same issues were actually
litigated in the High Court. For instance. Teva contends, the
parties fully aired all factual evidence, where both sides had
S2la
qualified expert witnesses to explain the evidence to the
Court. Further. Teva argues that all witnesses appeared live
and were extensively cross-examined and after the trial both
parties provided written submissions and appeared for
extensive argument before Justice Jacob. As a result, Teva
argues. Merck cannot contend that these issues were not
litigated.
Fourth. Teva argues that the issues were determined
by a valid and final judgment. Teva points out that the
judgment of the High Court was the “Approved Judgemenit
of that Court ~lt was issued on January 21, 2003 and
reissued in corrected form January 22. 2003. Teva notes that
Merck has appealed the judgment, but that fact does not
imply that the judgment is not final for purposes of collateral
estoppel. In fact. Teva argues that it is well settled that the
pendency of an appeal does not diminish the preclusive effect
of an appealed judgment. (D.I. 114 at 13) (quoting Rice v.
Department of Treasury. 998 F.2d 997, 999 (3d Cir. 1993)).
_ Lastly. Teva contends that the resolution of
obviousness was essential to the judgment in the High Court.
Specifically. it contends that Justice Jacobs was required to
~and did evaluate and interpret the prior art provided by
Merck's witnesses. and that, all findings on these issues were
necessary to his final judgment that the patent was invalid for
obviousness. Based on this. Teva argues that the High Court's
factual findings should be given preclusive effect.
y 2 Merck's Contentions
In response. Merck argues that there is no
transnational collateral estoppel as to the validity of a United
States Patent. First, Merck contends that Teva fails to point to
a single Federal Circuit case where, a foreign court's
judgment that the patent was invalid, or the factual
underpinnings of such a judgment, was given collateral
53a
estoppel effect in a case litigating the validity of a United
States Patent. In fact, Merck argues that the Federal Circuit
and its predecessor court have rejected such attempts. For
example in Meditronic Inc. v. Daig Corp., 789 F.2d 903 (Fed
Cir. 1986), cert. denied, 107 S. Ct. 402 (1986), the Federal
Circuit rejected the argument that it should adopt the
conclusion of a German tribunal that a German counterpart
was obvious and stated, “[t]his argument is specious. The
patent laws of the United States are the laws governing a
determination of obviousness/nonobviousness of a United
States patent in a federal court.” Id. at 907-908.
Additionally, Merck contends that the predecessor to
the Federal Circuit came to the same conclusion in In re
Duhlberg 472 F.2d 1394, 1398 (C.C.P.A. 1973) and In re
Larsen, 292 F.2d 531, 533 (C.C.P.A. 1961), where in both
cases, the court refused to consider the actions of a foreign
country's patent office with respect to the patentability of the
subject matter before the court.
Further, Merck argues that district courts have refused
to give collateral estoppel effect to a foreign court's
judgment. For example, Merck points to Cuno, Inc. vy. Pall
Corp., 729 F. Supp. 234 (E.D.N.Y. 1989), where the High
Court found the European counterpart of the United States
patent at issue to be valid and infringed, and when the
plaintiff sought to have the United States district court give
collateral estoppel effect to certain factual findings, the court
denied the request and stated. that:
Even if the court were to apply collateral estoppel to
certain factual findings made by the British Court -
as opposed to importing its legal conclusions
wholesale-it is not clear that the trial time would be
significantly shortened. Furthermore, the Federal
Circuit's reluctance to give collateral estoppel effect
Sda
to foreign judgments would seem to apply here to
foreign findings of facts insofar as those findings
involve mixed questions of fact and foreign law.
Id. at 238-239.
Moreover, Merck distinguishes the cases cited by
Teva. First. in regard to the Oneac case, Merck points out that
the court refused to give preclusive effect to questions of law
or mixed questions of law and fact, and to the extent that
certain factual findings were given collateral estoppel effect,
it was because both parties to the suit agreed to be bound by
those factual determinations. Oneac Corp., 20 F. Supp. 2d at
1242-1243. Additionally, Merck points to the Vas-Cath case
where the Northern District of Illinois adopted certain factual
findings of a Canadian Court in regard to the validity of a
patent. after parsing out the Canadian judgment, comparing
the relative Canadian and United States’ laws and making its
own conclusions regarding the applicability of the factual
determinations in the context of the United States’ legal
framework. Additionally, in the Northlake cases, Merck
points out that the district court adopted only certain factual
findings from a previous Belgian proceeding after careful
review of those findings and contends that most importantly,
the issues that were precluded limited the evidence that the
patent challenger could rely on. See Northiake Il, 986 F.
Supp. 475-476: Northlake I, 958 F. Supp. at 379.
Next. Merck argues that the requirements for
collateral estoppel have not been met. First, Merck contends
that the High Court's factual findings regarding obviousness
were not essential to the final judgment because the High
Court found that the '292 was invalid based on three grounds:
1) invalid as a method of treatment: 2) incapable of industrial
application: and 3) invalid as obvious- not obviousness alone.
(aA A A a a
5Sa
Lastly, Merck argues that the facts and applicable
legal standard is different. Specifically, Merck contends that
in the United States obviousness is ultimately a question of
law which rests on the foliowing factual inquiries: 1) the
scope and content of prior art: 2) the level of ordinary skill in
the art; 3) the differences between the claimed invention and
the prior art; and 4) objective considerations of
nonobviousness. See Advanced Display Systems, Inc. v.
Kent State Univ., 212 F.3d 1272, 1284-85 (Fed. Cir. 2000),
On the other hand, Merck argues, in Britain, wie
determination of obviousness is based on the following
factual inquiries: 1) identifying the inventive concept
embodied in the patent in suit: 2) assuming the mantle of the
normally skilled but unimaginative addressee in the art at the
priority date and impute to him what was, at that date,
common general knowledge in the art; 3) identifying what, if
any, differences exist between the matter cited as being made
available to the public and the alleged invention; 4)
determining whether, viewed without any knowledge of the
alleged invention, those differences constitute steps which
would have been obvious to the skilled man or whether they
required any degree of invention. (D.I. 126 at 17) (citing
Windsurfing International, Inc. v. Tabur Marine (Great
Britain) Ltd., 1985 R.P.C. 59, 60-61 (1985 -Ct. Of Appeal)).
Merck contends that although these standards are similar. the
United States Court is required to consider objective
considerations of obviousness, while in Britain they are not.
Accordingly, Merck contends that collateral estoppel is
improper.
te Discussion
As outlined above, the standards for determining
obviousness in the United States and Britain are different. In
fact, for purposes of this motion, Teva concedes that there
may be differences in the legal standards for validity between
56a
the United States and Britain. Additionally, after reviewing
the “factual findings” of the High Court, the Court finds that
many of the principles are mixed questions of law and fact.
The cases cited demonstrate that mixed questions of law and
fact should not be adopted if there are two different legal
standards, as in this case. See, e.g., Oneac Corp., 20 F. Supp.
2d at 1242-1243 (declining to adopt mixed questions of law
and fact). Additionally, in Oneac the court only adopted
factual findings from a foreign tribunal where the parties
agreed to be bound by such factual findings. Id. at 1242-43.
This is not the situation in the instant case because Merck
opposes any adoption of the High Court's factual findings.
Also, the Court finds that Merck has_ successfully
distinguished the Northlake cases from the instant case,
where in the Northlake cases the issues that were precluded
limited the evidence that the patent challenger could rely on
and the adopted factual findings did not go to the validity of
the patent in suit.
The Court also concludes that all of the elements
necessary for a finding of collateral estoppel are not present
in this case. Specifically, the High Court's factual findings
relating to obviousness were not essential to the High Court's
decision because that decision was based on three separate
grounds as detailed above. The Third Circuit has stated that
“if a judgment of a court of first instance is based on
determinations of two issues, either of which standing
independently would be sufficient to support the result, the
judgment is not conclusive with respect to either issue
standing alone.” Arab African Int'l Bank v. Epstein, 958 F.2d
532, 535, (3d Cir. 1992) (quoting Restatement (Second) of
Judgments § 27, cmt. i), rev'd in part on other grounds, 10
F.3d 168 (3d Cir. 1996). The Court concludes that based on
this standard, the High Court's finding of obviousness cannot
be said to be essential to the final determination.
57a
There may be cases where “the balance tips in favor
of preclusion because of the fullness with which the issue
was litigated and decided in the first action.” Masco Corp v.
United States, 303 F.3d 1329-1330 (Fed. Cir. 2002).
However, the Court concludes that this is not such a case,
especiaily in light of the fact that the Federal Circuit has
cautioned courts against giving too much weight to foreign
tribunals who are confronted with the same prior art. See
Heidelberger Druckmaschinen AG v. Hantscho Comm.
Prods... Inc.. 21 F.3d 1068, 1072 (Fed. Cir. 1994)
(recognizing that theories and laws of patentability differ
from country to country and Stating that “[cJaution is
required when applying the action of a foreign patent
examiner to deciding whether the requirements of 35 U.S.C.
§ 103 are met under United States law, for international
uniformity in theory and practice has not been achieved.”).
While the Court has reviewed Justice Jacob's factual findings
in regard to obviousness, based on the aforementioned
reasons, the Court declines to adopt them and will make
independent findings of fact on the issue of validity.
Accordingly, Teva's motion will be denied.
IV. Invalidity
Once issued a patent is presumed to be valid. See 35
U.S.C. § 282. The party challenging the patent bears the
burden of proving by clear and convincing evidence that the
patent is invalid. See Helifix Ltd. v. Blok-Lok Ltd., 208 F.3d
1339, 1346 (Fed. Cir. 2000). Clear and convincing evidence
is evidence that places in the fact finder “an abiding
conviction that the truth of [the] factual contentions are
‘highly probable.” Colorado v. New Mexico, #57 U.S. 310,
316 (1984),
Defendants contend that the '329 Patent is invalid and
therefore cannot be infringed. Defendants argue invalidity on
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two grounds: anticipation by the July 1996 Lunar News
reference under 35 U.S.C. § 102(e), and obviousness under
35 U.S.C. § 103. For the reasons set forth below, the Court
concludes that the '329 Patent is valid.
A. Claim C onstruction
The first step in any invalidity analysis is claim
construction which is an issue of law. SIBIA Neurosciences,
Inc. v. Cadus Pharmaceutical Corp., 225 F.3d 1349, 1355
(Fed. Cir. 2000); Markman v. Westview Instruments, Inc., 52
F.3d 967, 970-71 (Fed. Cir. 1995) (en banc), aff'd, 517 U.S.
370 (1996). A claim term should be construed to mean “what
one of ordinary skill in the art at the time of the invention
would have understood the term to mean.” E.g.. Markman,
S52 F.3d at 986. Further, when conducting a claim
construction analysis, a district court should be cognizant of
the fact that claims should be construed, if possible, to
uphold their validity. In re Yamamoto, 740 F.2d 1569, 1571
& n.* (Fed. cir. 1984) (citations omitted).
The starting point for a claim construction analysis is
the claims themselves. Vitronics Corp. v. Conceptronic, Inc.,
90 F.3d at 1582: see also Pitney Bowes, Inc. v. Hewlett
Packard Co., 182 F.3d 1298, 1305 (Fed. Cir. 1999) (stating
that “[t}he starting point for any claim construction must be
the claims themselves.”). Thereafter, the remainder of the
intrinsic evidence should be examined beginning with the
specification and concluding with the prosecution history.
Vitronics, 90 F.3d at 1582 (outlining this order for
examination in claim construction).
Generally, there is a strong presumption in favor of
the ordinary meaning of claim language as understood by
those of ordinary skill in the art. Bell Atl. Network Servs.,
Inc. v. Covad Communications Group, Inc., 262 F.3d 1258,
1268 (Fed. Cir. 2001). However, it is well-settled that a
59a
patentee may act as his own lexicographer and use the
specification to supply implicit or+ Jicit meanings for claim
terms. Bell Atl. Network Servs., : "3d at 1268 (Fed. Cir.
2001); Vitronics Corp., 90 F.3d at 1582: Markman, 52 F.3d at
980 (noting that patentee is free to be his own lexicographer,
but emphasizing that any special definitions given to words
must be clearly set forth in patent). “[T]he patentee's
lexicography must, appear ‘with reasonable Clarity,
deliberateness, and precision’ before it can affect the claim.”
Renishaw PLC v. Marposs Societa’ per Azioni, 158 F.3d
1243, 1249 (Fed. Cir. 1998) (quoting In re Paulsen, 30 F.3d
1475, 1480 (Fed. Cir. 1994)).
If the meaning of a claim term is clear from the
totality of the intrinsic evidence, than the claim may be
construed. If, however, the meaning of a claim term is
“genuinely ambiguous” after examining the intrinsic
evidence, than a court may consult extrinsic evidence. Bel] &
Howell Document Mgmt. Prods. Co. v. Altek Sys., 132 F.3d
701, 706 (Fed. Cir. 1997).
Claim terms in claims 23 and 37 of the '329 Patent are
disputed in this case. Accordingly, the Court will focus its
discussion on these claims
In full, claim 23 of the '329 Patent provides, “[a]
method according to claim 22 wherein said unit dosage of
said bisphosphonate comprises about 70 mg of alendronate
monosodium trihydrate on an alendronic acid active basis.”
(PTX 1, '329 Patent at col. 21, lines 24-27) (emphasis added).
In full, claim 37 of the '329 Patent provides, “[a]
method according te claim-36 wherein said bisphosphonate
unit dosage comprises about 35 mg of alendronate
monosodium trihydrate, on an alendronic acid active basis.”
(PTX 1, '329 Patent at col. 22. lines 24-26) (emphasis
added).
60a
Teva contends that the term “about” in claims 23 and
37 should be construed according to its ordinary meaning of
“approximately.” (D.I. 147 at 3). Merck contends that the
patentee in this case acted as his own lexicographer and set
out the meaning of “about” in the specification where the
specification explains that the term “about” accounts for the
variability of weight of the active ingredient that would result
from the use of different salts of alendronic acids. (D.I. 141
at 42). Thus, Merck contends that the phrase “about 70 mg”
as used in claim 23 and “about 35 mg” as used in claim 37
means 70 and 35 mg respectively of the active ingredient on
an alendronic acid active basis. Id. at 43. In other words,
Merck contends that, regardless of the final weight of the
actual active ingredient in the tablet, it contains the same
number of alendronate core molecules as 70/35 mg of
alendronic acid.
In rebuttal, Teva contends that Merck's proffered
construction makes no sense. Teva points out that according
to Merck, the word “about” is used to account for the fact
that different alendronate salts have different molecular
weights, and that to deliver the same amount of
physiologically active compound to the bone they must be
delivered at slightly different dosage strengths. (D.I. 147 at
4). Teva contends that Merck's interpretation is nonsensical
because the claim itself accounts for this phenomenon by
directing that the compound be administered on the basis of a
common denominator, i.e., “on an alendronic active basis.”
Id. In other words, Teva contends that the claims require that
the amount “alendronate sodium trihydrate” be sufficient to
deliver the same amount of active material as “about 70/35
mg” of alendronic acid. Id. As a result, Teva contends, the
term “about” does not perform the function which Merck
assigns to it, and must be in the claim for another purpose,
that is, to have its ordinary meaning of “approximately.”
6la
After reviewing the claim terms and the specification,
the Court concludes that the patentee explicitly and with
reasonable clarity and precision defined the term “about 70
mg” in claim 23 and “about 35 mg” to mean the equivalent of
70/35 mg of alendronic acid when taking into account
molecular weight variances for its derivatives that carry
accessories. Simply put, no matter what the final weight of
the actual active ingredient in the tablet is, it contains the
same number of alendronate core molecules as 70/35 mg of
alendronic acid.
The relevant portion of the '329 Patent specification
provides:
Because of the mixed nomenclature currently in use
by those or [sic] ordinary skill in the art, reference
to a specific weight or percentage of
bisphosphonate compound in the present invention
is on an active weight basis unless otherwise
indicated herein. For example the phrase “about 70
mg of bone resorption inhibiting bisphosphonate
selected from the group consisting of alendronate,
pharmaceutically acceptable salts thereof and
mixtures thereof, on an alendronic acid weight
basis” means that the amount of bisphosphonate
compound selected is calculated based on 70 mg of
alendronic acid.
PTX 1, the '329 Patent, col. 10, 65-col. 11, line 8. (emphasis
added). The Court concludes that the specification clearly
indicates that the terms “about 70 mg” and “about 35 mg”
refer to the fact that depending on the derivative of the
alendronic acid that could be used in the oral formulation,
different weights will be needed in order to get the same
effect as 70 or 35 mg of the seminal compound, alendronic
acid. As Merck points out, the alendronate sodium in
62a
Fosamax includes an atom of sodium metal for each
molecule of alendronate sodium. (D.1. 138 at 24). If a
formulator was to select a different salt which includes a
metal atom that is heavier than salt, e.g., a potassium or
barium atom, the total amount of material in each tablet
would have to increase if the amount of alendronic acid were
to remain the same. By conforming the weight of the
alendronate derivative in the claim of the '329 Patent to the
equivalent weight of the alendronic acid, a formulator can
consistently know how many basic units (alendronic acid
units) are to be used, even though the final total weight may
be different. Examples 7 and 8 of the '329 Patent reinforce
this conclusion. They provide for oral formulations
“containing about 35 mg” and “about 70 mg” of alendronate
“on an alendronic acid active basis.” The claims at issue use
the same phraseology and the ingredient tables in the
examples are consistent with the premise that “about”
accounts for the fact that alendronate derivatives have
accessories that add to the weight of the molecules. Thus, in
the examples “about 35 mg” turns out to be 45.68 mg of
alendronate monosodium trihydrate and the “about 70 mg”
turns out to be 91.35 mg of alendronate monosodium
—__——trihvdrate. See PTX 1, the '329 Patent col. 19 lines 13-15,
col. 19, lines 44-46, col. 19 lines 20-21, col. 19 lines 51-52.
Although the Court finds that Dr. Russell, is
competent in the area of bisphosphonates, it does not find his
z opinion as to the definition of the phrases “about 70/35 mg”
in the '329 Patent persuasive. During cross examination on
this issue, Dr. Russell testified as follows:
Q. Now is it true that when you deal with the claims
in this case, the claims recite 70 and 35; correct?
That is 70 mg a week and 35?
A. The claims say about 70 and about ....
Q. And what does “about” mean to you?
63a
A. Well about to me depends how precise a
definition we want. But for purposes of how close
the 40 and 80 are to about 35 and 70, I've given you
my opinion on that, that for practical purposes,
those would be the same, they would be
indistinguishable in their effects, given everything
else we know about the properties of these drugs.
Q. But the claim itself, what the claim really means,
is 70, not 80; correct?
A. It says about 70 and about 35.
Q. Did you read the patent, Dr. Russell, the entire
body of the patent?
A. Yes, I have.
Q. So in the patent, does it tell you what about 70
means?
A. There is a reference somewhere to about in the
patent as | recall, but I'd need to be directed to
where it was.
Q. Why don't you go to the first, in the patent,
which ~is Defendant's Exhibit 1 and Plaintiffs
Exhibit 1, at column 11, lines-about 1 through 9. It
says here in the definitional context exactly what
about 70 milligrams means: correct?
A. It- well, there's almost an intrinsic contradiction
in this, because the definition here is talking about
70, and then referring to whatever salt form is used
being referenced to the alendronic acid itself, yes.
Q. But in the patent it gives you a precise reference
and says when we say about 70 milligrams of a
bone resorption inhibiting bisphosphonate, what we
mean is that amount of a bisphosphonate that will
deliver an equivalent amount, the equivalent of 70
milligrams of alendronic acid: correct?
A. Yes. I have difficulty with this statement because
the reason if it's that precise at 70, why does it use
the phrase about?
64a
Q. But they gave you that exact definition; correct?
A. It's a curious use of the English language.
Q. | understand, but it is what it says, and perhaps
the person wanted to say if it's a certain salt one,
you might use 71, and if it's a certain salt 2, you
might use 73. Isn't that what's indicated in this?
A. Possibly.
Q. But that's what the definition says; right?
A. That is the definit it's described in tt
patent.
Russell at 337-339. (emphasis added). Although Dr. Russell
opined that the explicit definition of the disputed claim terms
in the specification was “a curious use of the English
Language,” he testified that Merck's proffered construction is
the definition as it is described in the patent. The Court finds
Dr. Russell's interpretation unpersuasive, especially in light
of the fact that patentees may give special meanings to claim
terms either explicitly or implicitly in patent specifications.
Further, with regard to Teva's claim that there is no function
to Merck's proffered construction, the Court finds this
argument unpersuasive given the clear directive in the
specification to construe the term “about 70/35 mg” to mean
the equivalent of 70/35 mg of alendronic acid when taking
into account molecular weight variances for its derivatives
and the fact that depending on the derivative of alendronic
acid used in the oral formulation, different weights will be
needed in order to get the same effect as 70 or 35 mg of
alendronic acid. See Bell Atl. Network Servs., 262 F.3d at
1268 (noting that the specification must express a clear intent
to redefine a claim term). Accordingly, the Court will accept
Merck's proffered construction and construe the disputed
claim terms “about 70/35 mg” to mean the equivalent of
70/35 mg of alendronic acid when taking into account
molecular weight variances for its derivatives that carry
65a
B. Anticipation
Anticipation is determined through a comparison of
the claim language with a single prior art reference. See
Wi v. nc., 209 F. Supp.
2d 348, 391 (D. Del 2002). In pertinent part, 35 U.S.C.§
102(e) (2) provides:
A person shall be entitled to a patent unless ...
(2) a patent granted on an application for patent by
another filed in the United States before the
invention by the applicant for patent, except that a
patent shall not be deemed filed in the United States
for the purposes of this subsection based on the
filing of an international application filed under the
treaty defined in section 351 (a).
35 U.S.C. § 102 (e) (2). Anticipation under 35 U.S.C. §
102 (€) requires that every element of the claim be found
either expressly or inherently “in a single prior art
reference.” In re Robertson, 169 F.3d 743, 745 (Fed. Cir.
1999). Thus, if the prior art reference does not expressly
State an element of the claim, “that reference may still
anticipate if that element is ‘inherent’ in its disclosure.”
Id. Inherency is established if the evidence makes “clear
that the missing descriptive matter is necessarily present
in the thing described in the reference and, and that it
would be so recognized by persons of ordinary skill.”
, 948 F.2d 1264,
1268 (Fed. Cir. 1991). Although inherency cannot be
established through probabilities, recognition by a person
of ordinary skill in the art before the critical date of the
patent is not required to show inherent anticipation.
Vv , 2003 U.S. App.
Lexis 15496 at *9-10 (Fed. Cir. August 1, 2003)
(rejecting the contention that inherent anticipation
66a
requires recognition in the prior art before the critical
date); In_re Robertson, 169 F.3d at 745 (noting that
inherent anticipation cannot be demonstrated through
probabilities).
1. The Parties' Contentions
Teva contends that a July 1996 Lunar News article
expressly anticipates claims 23 and 37 of the '329 Patent.
Teva points out that since Merck has stipulated that it does
not assert an invention date before July, 22, 1997, the July
1996 Lunar News is prior art under 35 U.S.C. § 102(a). (D.1.
143 at 19). Further, Teva points out that although it has the
burden of proving invalidity by clear and convincing
evidence, that burden is more easily met in this situation
because Merck failed to provide the PTO with the July 1996
Lunar News.
Teva contends that the July 1996 Lunar News
discloses every element of claims 23 and 37 of the '329
Patent. Teva points out that claim 23 defines a method of
treating osteoporosis which comprises of oral administration
of “about 70 mg” alendronate monosodium trihydrate, on an
active alendronic acid basis, once-weekly. Similarly, Teva
argues the July 1996 Lunar News discloses the same
elements where it discusses the use of bisphosphonates,
including alendronate, “in dealing with osteoporosis,” which
means the treatment and prevention of osteoporosis. (D.I.
143 at 21; Russell at 137). Further, Teva contends that the
July 1996 Lunar News also specifies that the alendronate
therapy it is discussing includes “oral” alendronate therapy,
and that the term “alendronate” refers to “Fosamax by
Merck.” Teva also contends that the active ingredient of
Fosamax was well known to be alendronate monosodium
trihydrate, and the doSage strength of Fosamax was known to
be reported on an alendronic acid basis. (D.I. 143 at 21; DTX
67a
394; Russell at 138-39). Teva also points out that the article
specifies that the drug can be administered on a weekly basis
at a dose of 80 mg where it states that, “ ... oral alendronate
potentially could be given in a 40 or 80 mg dose once/week.”
(D.I. 143 at 21) (quoting DTX 418 at 23). Teva directs the
Court to Dr. Russell's testimony where he opines that to a
person skilled in the art, 80 mg of alendronate once per week
is clinically indistinguishable from 70 mg once a week, and
is therefore “about 70 mg.” (D.I. 143 at 21: Russell at 138).
Teva also contends that Merck itself viewed 80 mg and 70
mg as the same weekly dose. (D.I. 143 at 21; DTX 147 at
MK0158265). Thus, Teva contends the July 1996 Lunar
News Article discloses every element of claim 23: treatment
of osteoporosis by the administration of about 70 mg
monosodium trihydrate on an alendronic acid basis once-
weekly. (D.I. 143 at 22).
Teva further contends that the July 1996 Lunar News
anticipates claim 37 of the '329 Patent. Claim 37 claims a
method for preventing osteoporosis in a human being
comprising of orally administering about 35 mg of
alendronate sodium on an alendronic acid basis as a unit
dosage according to a continuous schedule having a dosage
interval of once-weekly. (D.I. 143 at 22; DTX 1). Teva points
out that the only difference between the two claims is that
claim 23 is directed to “treatment” of osteoporosis with a 70
mg weekly dose, and claim 37 is directed to “prevention”
with a 35 mg weekly dose. Teva reiterates the contention that
the July 1996 Lunar News deals with both the treatment and
prevention of osteoporosis and discloses the use of a 40 mg
once-weekly oral dose. (D.I. 143 at 22). Teva again directs
the Court to Dr. Russell's testimony where he testified that to
a person skilled in the art, a 40 mg dose of alendronate once
per week is clinically indistinguishable from 35 mg once per
week and is therefore “about 35 mg.” (D.I. 143 at 22: Russell
at 140; DTX 147 at MK0158265). As a result, Teva contends
68a
that the July 1996 Lunar News discloses every element of
claim 37: prevention of osteoporosis by oral administration
of about 35 mg alendronate monosodium trihydrate on an
alendronic acid basis once weekly. (D. 1. 143 at 22).
Teva contends that Merck's “fear defense” is
irrelevant to anticipation. First, Teva points out that claims 23
and 37 do not require that once-weekly administration of
alendrcnate meet any standard of safety or tolerability. (D. I.
143 at 23). Even if they did, Teva argues, such a requirement
would not avoid anticipation because the property of
tolerability is inherent in the method disclosed in prior art.
Further, Teva argues that the concept of “teaching away”
from an invention is inapplicable in an anticipation analysis,
and therefore, the Court should not consider it. (D.I. 143 at
24). Based on this, Teva contends that claims 23 and 37 are
anticipated by the July 1996 Lunar News, and are therefore,
invalid.
In reply, Merck contends that the July 1996 Lunar
News fails to anticipate claims 23 and 37 of the '329 Patent.
Merck points out that the claims require the use of 70 or 35
mg of alendronate sodium on an alendronic acid active basis
and even if one were to read the July 1996 Lunar News
suggestion that “[e]ven alendronate potentially could be
given in a 40 or 80 mg dose once/week” as referring to the
amount on an alendronic acid active basis, 80 mg is not the
same as 70 mg and 40 mg is not the same as 35 mg. Merck
argues that the unambiguous weight requirement for
alendronate in claims 23 and 37 is not met by the Lunar
News’ suggestion of 80 or 40 mg, and therefore, it fails to
anticipate claims 23 and 37. (D.I. 138 at 27). Further, Merck
argues that the July 1996 Lunar News is not enabling, and
therefore, cannot anticipate. Specifically, Merck contends
that in order for a disclosure to be enabling it must allow one
of skill in the art to practice the invention, and the July 1996
69a
Lunar News falls short of this standard because it fails to
address the expectation by physicians in the field during
1996-1997 that alendronate sodium at doses over 20 mg
would not be well-tolerated in the prevention and treatment
of osteoporosis. Merck points to Dr. Fennerty's testimony to
establish that a knowledgeable gastroenterologist during the
applicable period would have been “extraordinarily
concerned” about suggesting 40 or 80 mg of alendronate to
treat osteoporosis. (D.I. 138 at 28: Fennerty at 270-271).
Further, Merck argues that Dr. Papapoulos, Merck's
expert with extensive bisphosphonate and clinical
Osteoporosis experience, corroborates this sentiment. (D.I.
138 at 28). Merck argues that given the state of the medical
knowledge at the time. a physician would not administer
those high dosages when managing Osteoporosis, and as a
result, the July 1996 Lunar News fails to anticipate claims 23
and 37 of the ‘329 Patent.
2. Whether the July 1996 Lunar News
Anticipates the '329 Patent
After a review of the record evidence, the Court
concludes that claims 23 and 37 of the ‘329 Patent are not
anticipated under 35 U.S.C. § 102(e) (2). Specifically, the
Court concludes that Teva has failed to prove by clear and
convincing evidence that the July 1996 Lunar News
expressly or inherently discloses the dosage amounts for
alendronate in claims 23 and 37. As a threshold matter and
contrary to Teva's contentions, it has to prove invalidity by
clear and convincing evidence. See American Hoist &
Derrick Co. v. Sowa & Sons, Inc., 725 F.2d 1350, 1360 (Fed.
Cir. 1984) (citations omitted) (stating that when a challenger
Produces prior art not before the PTO “the standard of proof
does not change; it must be by clear and convincing evidence
70a
or its equivalent.”) With this standard in mind, the Court will
consider the parties’ contentions with regard to anticipation.
The Lunar corporation was a manufacturer of bone
densitometry equipment, which is a diagnostic tool for
osteoporosis. (Russell at 129). The Lunar News was a
quarterly newsletter distributed by the Lunar Corporation to
its customers. (Mazess Dep. at 55-56; Russell at 129). It was
authored by Dr. Richard Mazess', the former President of the
Lunar Corporation. The July 1996 edition’ contained a
section entitled, “Update Bisphosphonate,” (PTX 29 at 23).
The section discusses bisphosphonates as a treatment for
osteoporosis. Id. Specifically, in reference to the use of
alendronate for treatment of osteoporosis, it states that
“{s]ome United States physicians are reluctant to treat
because of: a) side effects; b) difficulty of dosing; and (c)
high costs ($700/year). (PTX 19 at 23). To address the
difficulty of dosing and high costs the article suggests:
The difficulties with oral bisphosphonates may
favor their episodic (once/week) or cyclical (one
week each month) administration. Even oral
alendronate potentially could be given in a 40 or 80
' Dr. Mazess does not possess an MD, has no formal training in
pharmacology, and obtained his bachelors degree and Ph.D. in
anthropology. (Mazess Dep at 30-32).
The Court understands that Teva is not contending that the April
1997 edition of the Lunar News anticipates the '329 Patent. See D.I. 143;
Opening Brief at 19-24 (failing to assert that the April 1997 Lunar News
anticipates claims 23 and 37 of the '329 Patent). However, even if Teva
made this assertion, the Court concludes that the April 1997 Lunar News
did not anticipate claims 23 and 37 because it does not suggest any
dosage amounts in connection with its discussion of once-weekly dosing
of alendronate. (DTX 417). Thus, it does not disclose all of the elements
of claims 23 and 37, namely “about 35/70 mg” of alendronate, and
therefore, cannot anticipate the claims either expressly or inherently.
7la
mg dose once/week to avoid dosing problems and
reduce costs.
PTX 29 at 23. Teva contends that the July 1996 Lunar News
article discloses all of the elements in claim 23 of the ‘329
Patent. Specifically, Teva argues that the July 1996 Lunar
News discloses the following elements: 1) A method of
treating Osteoporosis in a human; 2) orally administering; 3)
about 70 mg; 4) of alendronate monosodium trihydrate; 5) on
an alendronic acid active basis; 6) as a unit dosage; and 7)
according to a continuous schedule having a dosing interval
once-weekly. (D.I. 143 at 23). Merck asserts that the July
1996 Lunar News article does not anticipate claim 23
because it fails to reference 70 mg of alendronate sodium on
an alendronic acid active basis as required by claim 23. (D.1.
141 at 44).
After reviewing the July 1996 Lunar News in light of
the '329 Patent, and the Court's construction of the claim
terms, the Court is not persuaded that Teva has demonstrated
by clear and convincing evidence that claims 23 and 37 of
the '329 Patent are anticipated by the July 1996 Lunar News.
The July 1996 Lunar News fails to reference 70 _mg of
alendronate sodium on an alendronic acid basis as required
by the claim. Instead it references an 80 mg dose of oral
alendronate. Thus, it does not expressly disclose “about 70
mg” of alendronate sodium “on an alendronic acid basis.”
Likewise, the Court is not persuaded that Teva has
demonstrated inherency. Although Dr. Russell testified that
80 mg and “about 70 mg” are the same for all practical
purposes because they have the same effect on patients, he
did not testify that this element was “necessarily present” in
the July 1996 Lunar News reference or that its disclosure was
sufficient to show that this element was the natura! result
flowing from the operation as taught. In fact, in the Court's
view, Dr. Russell's testimony was insufficient on this issue,
J2a
and was, at best, conclusory. For example, although Dr.
Russell testified that 80 mg and 70 mg are the same for all
practical purposes because they would have the same effect,
the Court recognizes that in rendering his opinion Dr. Russell
did not take into account the Court's construction of the term
“about 70 mg”™. (Russell at 137-139). Further, the Court notes
that Dr. Russell provided no evidence to support his
conclusion that 70 and 80 mg were equivalent. In fact, Dr.
Papapoulos testified on cross-examination that one would
need to test the 80 and 70 mg doses before concluding with
any certainty that they are the same and the regulations
regarding the filing of an ANDA recognize that any change in
the dosage of a drug would require additional data.
(Papapoulos at 676-678; 21 U.S.C. § 355 (j(2); 21 C.F.R. §
314.93). Dr. Russell, provided no such data. Based on this,
the Court concludes that Teva has failed to demonstrate that
the July 1996 Lunar News inherently or expressly disclosed
the element of “about 70 mg” of alendronate sodium “on an
alendronic acid active basis” as required by claim 23 of the
‘329 Patent.
Similarly, the Court concludes that the July 1996
Lunar News fails to disclose “about 35 mg” as required by
claim 37 of the '329 Patent. Specifically, the July 1996 Lunar
News fails to reference “35 mg” of alendronate sodium “on
an alendronic acid active basis” as req_ red by the claim.
Although it references “40 mg”, in light of the Court's claim
construction of “about 35 mg” to mean the equivalent of 35
mg of alendronic acid when taking into account molecular
weight variances for its derivatives that carry accessories, the
Court concludes that the July 1996 Lunar News reference
does not expressly disclose “about 35 mg” as required by
claim 37. Likewise, the Court concludes that Teva's
inherency argument as to claim 37 must also fail. Dr. Russell
testified that a 40 mg dose is about the same as a 35 mg for
all practical purposes. (Russell art 140-141). However, the
73a
Court finds Dr. Russell's opinion on this issue to be
conclusory because he provides no evidence, statistical tests
or data to support this assertion. Further, Dr. Russell did not
testify that this element was “necessarily present” in the July
1996 Lunar News reference or that its disclosure was
sufficient to show that this element was che natural result
flowing from the Operation as taught. Based on this, the
Court finds that the evidence is insufficient to show that each
element of claims 23 and 37 of the 329 Patent were present
in the prior art reference expressly or inherently. Accordingly,
the Court concludes that Teva has failed to establish by clear
and convincing evidence that the '329 Patent was anticipated
by the July 1996 Lunar News. Because the Court concludes
that claims 23 and 37 of the '329 Patent were not anticipated
by the July 1996 Lunar News, the Court will not address the
parties’ contentions concerning enablement of the prior art.
ad Obviousness
Teva contends that the '329 Patent is invalid, under 35
U.S.C. § 103, as obvious. In pertinent part, 35 U.S.C. § 103
provides that a patent may not be obtained “if the differences
between the subject matter sought to be patented and prior art
are such that the subject matter as a whole would have been
obvious to a person having ordinary skill in the art ..” 35
U.S.C. § 103. The obviousness determination is a question of
law which is based on several underlying factual inquiries.
See Richardson-Vicks Inc, v. U ohn Co., 122 F.3d 1476.
1479 (Fed. Cir. 1997). The underlying factual inquiries
require consideration of the four “Graham” factors which are:
(1) the scope and content of the prior art; (2) the differences
between the claims and the prior art; (3) the level of ordinary
skill in the pertinent art; and (4) any secondary
considerations of nonobviousness such as commercial
success, long felt but unsolved need. failure of others, and
acquiescence of others in the industry that the patent is valid.
74a
See Graham v. John Deere Co. of Kansas City, 383 U.S. 1,
~ 17-18 (Fed. Cir. 1996). Additionally, as with anticipation, the
burden of demonstrating obviousness is with the challenger
and invalidity must be proven by clear and convincing
evidence. C.R. Bard, Inc. v. M3 Systems, 157 F.3d 1340,
1351 (Fed. Cir. 1998).
1. The Parties’ Contentions
Teva contends that the ‘329 Patent is invalid as
obvious because both the April 1997 and July 1996 editions
of Lunar News explicitly disclose the weekly administration
of alendronate for osteoporosis and a person skilled in the art
would have understood in July 1997 that the weekly dose for
treatment and prevention of osteoporosis should be “about 70
mg™ and “about 35 mg” respectively, and that these doses are
explicitly set out in the July 1996 Lunar News. Teva argues
that not only did the Lunar News disclose the concept of
once-weekly dosing and provide the appropriate dose, a
person of ordinary skill would have predicted the Lunar
News teaching to be effective. (D. I. 143 at 26).
Further, Teva contends that there was a motivation to
employ once-weekly dosing because of the inconvenience of
the dosing regimen which consisted of taking the tablet
before eating, remaining upright for a half an hour and taking
the tablet with a full glass of water. Id. at 27. Teva points out
that the April 1997 and July 1996 editions of Lunar News
explicitly stated the motivation to administer alendronate
weekly; to improve patient convenience and compliance with
the dosing instructions. Id. Thus, Teva argues that the prior
art that claimed the invention also disclosed the motivation to
make it. Id.
Teva contends that a person of skill in the art would
not have been deterred from once-weekly dosing because of
the fear of increased gastrointestinal side effects. Id. As to
75a
this point Teva argues that the early reports of esophagitis
would not have deterred a person of skill in the art from
once-weekly dosing because the early reports showed that
these events were rare. occurring in one out of every ten
thousand patients taking 10 mg of alendronate daily, and that
these effects were for the most part reversible with proper
treatment. Id. at 28; Markowitz at 436-37; 451. Teva also
points out that in March 1996. five months after the launch cf
10 mg daily alendronate tablet. ten million patients had been
prescribed the tablet and fifty cases of severe esophagitis had
been reported to Merck. and Merck took no action until it
learned that a letter written by a well-known bone-specialist
discussing two such cases was circulating within the Mayo
Clinic Health System. D.I. 143 at 29: Hirsch Dep. at 54-56).
When it finally took action, Teva argues, Merck's
investigation concluded that the pill esophagitis cases were
caused primarily by the failure of patients to adhere to the
dosing instructions. (D.I. 143 at 29; Markowitz at 442:
Hirsch Dep. at 66; 82-84),
Teva also points out that in March 1996, Merck
disseminated a “Dear Doctor” letter, informing physicians
Paper reported that 51 patients experienced adverse effects
classified as “serious” or “severe” out of the 470,000 patients
worldwide who had received Prescriptions for alendronate to
treat Osteoporosis up to that time. (D. I. 143 at 30). Teva
—_
De Groen et al., The New England Journal of Medicine, 1996 (PTX
91).
76a
directs the Court to its gastroenterology expert, Dr. David
Markowitz. who testified that the extremely low incidence of
these effects. and the description of the cases, led
gastroenterologists to conclude at the time that the likely
cause of the probiem was “pill esophagitis.“(D.1. 143 at 30;
Markowitz 435, 438). -Teva argues that the evidence
presented at trial leads to the conclusion that once-weekly
administration would have been expected to decrease the
incidence of Severe esophagitis cases because it would: 1)
improve patient compliance with the dosing instructions
(Russell at 195-96; Markowitz at 485-86; Fennerty at 311);
and 2) decrease the frequency of administration, thereby
decreasing the chances of the tablet “sticking” in the
esophagus (Russell at 196-197; Markowitz at 443).
Teva also asserts that the evidence presented at trial
does not support a dose-response relationship between
alendronate and- gastrointestinal effects that would have
deterred a person of ordinary skill in the art from once-
weekly dosing. (D.1. 143 at 32). For example, Teva argues
that the results of the Chestnut* study related to daily and not
weekly dosing and demonstrated that 90% of
postmenopausal women with osteoporosis tolerated the 40
mg daily dose..Id. at 34. Also, Teva contends that Dr.
Fennerty's testimony regarding a dose-related relationship
was discredited by Merck's pre-litigation behavior and directs
the Court to the testimony of Dr. Markowitz who testified
that his contemporaneous investigations indicated that severe
events were extremely rare with alendronate and that overall
the drug was well tolerated. Id. at 35.
In addition, Teva contends that before this litigation,
Merck admitted that prior art data available in July 1997
fromm Paget's patients showed that once weekly dosing would
* Chestnut et al.. The American Journal of Medicine, 1995, (PTX 69).
77a
be well-tolerated. For example, Teva directs the Court to a
May 1997 “Tactical PAC” review seeking management
approval to go forward with the once-weekly dosing program
where it stated that “the 40 and 80 mg doses were well-
tolerated even when given on a daily basis.” (D.1. 143 at 39.
DTX 147 at MK0158265). Further, Teva points out that
Merck, in a formal submission to the FDA maintained that
data from Paget's disease provided an expectation that once-
weekly doses would be well tolerated. (D.1. 143 at 39: DTX
192 at 17).
Teva also argues that a person of skill in the art would
not have been deterred from once-weekly dosing because of
the alleged dose-related effects of prior art bisphosphonates,
because the magnitude of data available on alendronate in
treating Osteoporosis and Paget's disease made reference to
other bisphosphonates unnecessary. (D.I. 143 at 41). Teva
also points out that Merck's Physician Survey conducted in
1997 indicated that physicians perceived that larger less-
frequent doses would result in “less-GI upset.” (D.I. 143 at
43; DTX 244 at MK0174861).
Teva also contends that the '329 invention did not
provide unexpected results because the prior art disclosed its
principal advantage; convenience and compliance. (D.1. 143
at 44). Additionally, Teva contends that Merck did not carry
its burden of demonstrating commercial success because it
was required to show that the once-weekly product
contributed to the incremental success beyond the daily
product and that Merck's expert, Dr. Vellturo failed to
demonstrate any connection between the patented invention
and Merck's sales of once-weekly Fosamax. Specifically,
Teva contends that Dr. Vellturo did not opine that the two
were connected but merely asserted that “commercial success
could be at least in part, Significant part, attributable to the
Daifotis patients.” D.1. 143 at 48; Vellturo at 715. Further.
78a
Teva suggests that Dr. Vellturo's analysis is flawed because of
his emphasis on sales and prescriptions as the only indicia of
success without considering any other market factors such as
the increased awareness about osteoporosis and the effect of
the increasing number of Americans over the age of sixty,
like its own expert, economist, Dr. Richard Rozek took into
account. (D.1. 143 at 48). Additionally, with regard to
commercial success, Teva contends that Merck ignored its
own successful marketing efforts such as its heavy
promotional expenditures during the applicable period when
examining the commercial success of the once-weekly dose
of alendronate. (D.1. 143 at 51). Finally, Teva argues that Dr.
Vellturo's diffusion model is flawed because a diffusion
model in not particularly useful as a forecasting devise, and
therefore, its use in this context is inappropriate and
alternatively argues that Dr. Vellturo's use of the model is
incorrect. (D.1. 143 at 54).
In response, Merck contends that the once-weekly
high dose regimen of the '329 Patent was not obvious to a
skilled practitioner in 1997 because without hindsight, the
overwhelming knowledge in the field was that high oral unit
doses would not be safe and tolerable for osteoporotic
women. Merck points out that Dr. Russell, Teva’s expert,
acknowledged that a person of ordinary skill “would be
familiar with publications in the field and the technical
background in this field of bisphosphonates and
osteoporosis.” (Russell at 144). Thus, according to Dr.
Russell’s interpretation of one of ordinary skill, Merck
argues, a skilled practitioner would know that: 1) etidronate
and clodronate caused gastrointestinal side effects at high
doses; 2) pamidronate caused dose-related gastrointestinal
side effects that even led to the discontinuation of its
development as an oral medication; 3) alendronate caused
dose-related gastrointestinal side-effects; and 4) alendronate
sodium, even though proven to be safe and tolerable at 10
79a
and 5 mg doses, could still potentially cause severe upper
gastrointestinal injuries. (D.I. 145 at 10-11) (citations
omitted). Merck contends that the overwhelming knowledge,
laid out by contemporaneous publications in respected peer-
reviewed medical journals establishes that the pre-invention
expectation by those skilled in the art was that one could not
use alendronate sodium at unit doses higher than 20 mg for
the management of osteoporosis. Id. at 11.
Further, Merck asserts that Teva's “spin” on the
Chestnut study is flawed. Specifically, Merck points out that
in the Chestnut study only one out of sixty two women
(1.6%) withdrew from the 10 and 5 mg doses, but seven out
of sixty three women (11.1 %) withdrew from the 40 mg
alendronate treatment. Id.; PTX 69 at 150; Markowitz at 479-
482; Fennerty at 266. Moreover, contrary to Teva's assertion.
Merck points out that it informed the FDA that the Chestnut
Study had led it to “limit the maximum dose to 20 mg in
subsequent osteoporosis treatment studies.” (D.I. 145 at 15:
PTX 202 at MK250180: PFF 66). Additionally, Merck
asserts that as Dr. Papapoulos testified, a skilled practitioner
at the time knew that in actual clinical practice 10 to 12
percent of patients discontinued 10 mg Fosamax treatment
because of gastrointestinal side effects. (D.I. 145 at 12:
Papapoulos at 651-652). Thus, Merck argues that any
reasonable clinician, viewing this data could compare these
ratios and would expect the discontinuation rate for
osteoporotic women in actual practice, outside the confines
of a controlled clinical environment, to have been
unacceptably high at a 40 mg dose. Merck asserts that Teva
failed to consider that clinical studies are different than daily
practice and that discontinuations are far less common in the
context of a clinical study. (D.I. 145 at 12: PFF 60; Fennerty
at 262-64).
80a
In reference to Teva's reliance on internal and FDA
submitted documents, Merck contends that these publications
as presented by Teva were taken out of context, and
therefore, do not bolster Teva's argument with regard to
obviousness. Merck argues that Teva improperly relied on
these documents because these documents reflect the
inventors’ rationales to overcome the skepticism about high
unit doses and the inventors’ insights about their own
invention. In regard to extrapolating results from the Paget's
disease experience to doses for osteoporosis, Merck points
out that Professor Fleish's book, which Dr. Russell later
edited, reflected the thinking in the art that the tolerability for
alendronate sodium appeared to be higher for the pagetic
disease population than the osteoporosis population. (D.1.
145 at 15).
Merck also contends that it has never disputed that it
was known that once-weekly dosing would be efficacious in
providing the alendronate sodium needed to inhibit bone
resorption, but notes that it was the safety concern about high
oral doses (higher than 20 mg) that obscured the
advantageous once-weekly invention for the management of
osteoporosis. (D.I. 145 at 15). Further, Merck points out that
it did not rely on the case reports such as De Groen as
evidence of a dose-response, rather, Merck claims, the case
reports simply raised the awareness of physicians that
alendronate sodium was a potentially dangerous agent and
that Teva's expert, Dr. Markowitz admitted that the case
reports were clinically significant. (D.1. 145 at 18; Markowitz
at 468). Merck also rebuts the contention that it took no
action in resporise to the case reports and points out that it
promptly obtained data about each case, constructed a data
base and organized a meeting with Dr. De Groen and other
consultants by March 1996. Then, on March 15, 1996 Merck
sent out a “Dear Doctor” letter informing physicians about
the potential upper gastrointestinal injuries and emphasizing
8la
the importance of following directions in order to minimize
them. Merck also undertook internal studies to understand
the problem, including dog studies. (D.I. 145 at 19: PTX 67:
PFF 88).
In reference to Dr. Fennerty's testimony, Merck
contends that Teva mischaracterized his testimony regarding
the Blank® article. Merck asserts that the Blank study
provided a glimpse as to what happens when the use of
amirnobisphosphonates is combined with Non-Steroidal Anti-
Flammatory Drugs (“NSAIDs”) such -as aspirin and
ibubrofen. This study was published during February of 1997
in the peer reviewed Digestive Diseases and Sciences, and it
showed clear dose-related upper gastrointestinal injuries from
alendronate sodium when it was combined with the NSAID
indomethacin in a rat model. (D.I. 145 at 20; PTX 104 at 284
fig. 3). Merck contends that Dr. Fennerty observed that when
placed in the mosaic of prior art showing the dose dependent
injuries from bisphosphonates, the Blank study was
important to gastroenterologists, and he never retreated from
this position. (Fennerty at 270, 292-94). Additionally, Merck
points out that Teva itself stated to the PTO in 2000, in an
attempt to gain the issuance of claims for a delayed gastric
release alendronate formulation, that bisphosphonates as a
class exhibit side effects that “consist of irritation of the
upper gastrointestinal mucosa ... with the potential for this
irritation leading to more serious conditions.” (PTX 301,
U.S. Patent No. 6,476,006 (“the '006 Patent”) at col. 3, lines
25-25). Merck contends that Teva also told the PTO that the
“larger” once weekly doses have “the potential of
exacerbating the upper GI side effects of the drug.” D.I. 145
at 21 (quoting the ‘006 Patent at col. 3, lines 12-14).
* Blank et al., Digestive Diseases and Sciences, 1997 (PTX 106).
82a
Merck argues that Teva's reliance on the 1997
Physicians Survey is misplaced because it did not address the
use of higher doses. Specifically, Merck points out that at
issue is the invention of administering seven-fold the daily
dose of alendronate sodium once a week, and in the survey, a
twice-weekly dosing schedule was inquired about along with
other choices that included placing alendronate sodium in
diet colas and cranberry juice. (D.I. 145 at 22; DTX 244 at
174866). Merck points out that the invention of the '329
Patent does not lie solely in the less frequent dosing, but in
the fact that an entire weekly complement of daily doses
could be administered as a single unit dose and that the
marketing survey inquired about twice weekly dosing
without any mention of increasing the dose. Therefore,
Merck argues that it does not bear any relevance to the
invention of once-weekly dosing at sevenfold the daily dose.
(D.1. 145 at 22).
In regard to secondary considerations, Merck
contends that contrary to Teva's assertion that commercial
success is irrelevant in the obviousness inquiry because
Merck was the only entity allowed to market alendronate
sodium tablets, its direct competitors, including Procter &
Gamble, had an incentive to develop an improved dosage
form. (D.I. 145 at 23). Further, in reference to commercial
success, Merck contends that the increased sales for the
Fosamax franchise upon the launch of the once-weekly
dosing regimen is dramatic regardless of which way it is
viewed. (D.1. 145 at 25). Specifically, Merck points out that
the Fosamax franchise sales followed a constant increase
trend from 1996 until the introduction of once-weekly
Fosamax in 2000, where if the trend established before the
once-weekly dose was introduced had continued, an increase
of 18.9% over the prior year would have resulted. However,
after the once-weekly dosing was introduced, a dramatic
increase of 42.5% was realized. (D.1. 145 at 26; PTX 166;
83a
Vellturo at 718-720). Additionally, Merck contends that
Teva's attempt to discredit Dr. Vellturo's diffusion model was
unsuccessful. Merck argues that, in any event, Dr. Vellturo
testified that his opinion regarding the commercial success of
the '329 Patent was not based on model, but on a
fundamental shift in the constant trends he observed
regarding the Fosamax franchise's sales increases, market
share, prescription volume and on an evaluation of the
market share and prescription volume data for the
Osteoporosis market as a whole, and that the diffusion model
only confirmed the opinion he formed based on the
aforementioned factors. (D.1. 145 at 26: Vellturo at 718-728,
735; 755-757). Finally, Merck notes that Dr Rozek, Teva's
expert on obviousness, provided no ultimate conclusion
about the commercial success of the once-weekly dosing of
Fosamax or any of the factors he believed Dr. Vellturo should
have considered. (D. I. 145 at 26).
2. Whether the '329 Patent Was Obvious
in View of the Prior Art
After reviewing the relevant prior art in light of the
evidence and the factors related to the obviousness inquiry,
the Court concludes that Teva has failed to establish by clear
and convincing evidence that the '329 Patent was obvious in
light of the prior art references. The Court in its obviousness
analysis must be cognizant of “hindsight syndrome.” In re
Warner Kotzab, 217 F.3d 1365, 1369-1370 (Fed. Cir. 2000).
The Federal Circuit has instructed that, “the best defense
against the subtle but powerful attraction of a hindsight-based
obviousness analysis is rigorous application of the
requirement for a showing of the teaching or motivation to
combine prior art references.” In re Gartside. 203 F.3d 1305;
1329 (Fed. Cir. 2000). Therefore, in order to establish
obviousness from a combination of elements disclosed in
prior art, “there must be some motivation. suggestion or
84a
teaching of the desirability of making — the specific
combination that was made by the applicant.” Kotzab, 217
F.3d at 1370. With this standard in mind, the Court will
discuss the relevant factors of the obviousness inquiry as they
relate to the '329 Patent.
i. Level of One Skilled in the Art
For the purposes of the obviousness inquiry, the Court
finds that at the time of the filing of the '329 Patent, a person
of ordinary skill in the art was an individual who would have
an M.D. andor Ph.D. and was working in the field of and
doing research on osteoporosis. Such a person would be
familiar with the publications and technical literature and
background in the field of bisphosphonates and osteoporosis.
(D.1. 142 at 17-18: D.I. 141 at 41). The Court bases this
finding on a combination of Merck and Teva's proffered
interpretation of one skilled in the art and finds that there are
no significant differences between the two proffered
definitions.
ii. Scope and Content of Prior Art
At the outset. the Court notes that Merck has never
disputed that it was known that once-weekly dosing would be
efficacious in providing the alendronate sodium needed to
inhibit bone resorption. (D.I. 145 at 15). However, Merck
contends that it is the safety concern about high oral doses,
specifically unit doses higher than 20 mg, that obscured the
advantageous once-weekly invention for the management of
osteoporosis. Id. Thus. the issue is when viewing the mosaic
of the prior art. whether those of ordinary skill in the art
would have had the motivation to formulate a once-weekly
seven-fold daily dose of alendronate sodium, despite safety
concems.
8Sa
The Court concludes that the history of
bisphosphonates as a class is minimally relevant to the
instant discussion because although alendronate is a
bisphosphonate and general knowledge of bisphosphonates is
certainly within the knowledge of one of ordinary skill in the
art during the relevant time period, it was also well known
that each bisphosphonate had its own unique characteristics.
(See DTX 547 at 543) (Dr. Papapoulos, Merck's expert,
noting that because of differences in mechanisms of action
and pharmacological and toxicological profiles, it is
“important that specific properties of every individual
bisphosphonate be determined and that results obtained with
one bisphosphonate not be extrapolated readily to the whole
class.”). As a result, although the earlier bisphosphonates
etidronate, clodronate and pamidronate had dose related
gastrointestinal side effects, the Court concludes that this fact
holds little weight in its obviousness analysis given the
unique characteristics of each bisphosphonate, particularly
with side effects. (Papapoulos at 653-654; Russell at 384-
385; PTX 110 at 127, 129, 130; PTX 111 at 148, 149, 152:
PTX 112 at 154, 15, 1585; PTX 113 at 170, 171, 175: PTX at
289, E91, C278, C279).
Therefore, the Court will focus its discussion on the
prior art dealing with alendronate. The 1995, 1997. and 2000
editions of “Bisphosphonates in Bone Disease” written by
Professor Herbert Fleish, who is described as the “father of
bisphosphonates”, reported that oral alendronate sodium can
cause gastrointestinal disturbances at doses of 40 mg. (PTX
It] at 148; PTX 112 at 153; PTX 113 at 169; see also PTX
300 at 26). Further, in the 1997 and 2000 editions. Dr. Fleish
reported that a 40 mg dose may cause gastrointestinal
disturbances in patients with osteoporosis, but that the same
dose was well tolerated in patients with Paget's disease. (PTX
112 at 153; PTX 113 at 169).
R6a
Additionally, the Court finds that case reports are
prohative m its obviousness inquiry because, as Dr. Fennerty
testified, they offen contam mformation that would alter the
wav a physician would treat patients. (Fennerty at 247-248).
Case reports are publications usually involving one or a few
patients that have an outcome of clinical relevance or
importance. (Fennerty at 246-247). In October 1995, Maconi®
published a case report in the American Joumal_ of
Gastroenterology. which reported that an osteoporosis patient
after taking S mg of alendronate. had an endoscopy which
revealed severe damage to the esophagus. (Fennerty at 249-
280). Dr Fennerty testified that this case report was
significant because the particular journal it was published in
was “clinically relevant” and because this “severity of injury
had never heen reported in a patient taking a bisphosphonate
pnor to this. especially a bisphosphonate that was being used
mow very commonly in clinical practice as it had just been
released at about the time the case report was published.”
Fennerty at 250). In October 1996. De Groen published an
amicle in The New England Journal of Medicine which set
out three case reports describing the side effects of
alendronate sodium. (PTX 91). The first case report reported
that 2 ~3-vear-old woman developed chest pain and
gvsphagia after her first dose of 10 mg of alendronate
sadum. PTX 91 at 1016-1017). After two more doses she
was transferred to the Mavo Clinic where an endoscopy
revealed severe ulcerative esophagitis. (PTX 91 at 1017:
Fenner, at 254-56). The other two case reports revealed that
two addmonal women developed severe esophageal injury as
é result of taking 10 mg oral dose of alendronate sodium.
PTX 9) at 1017: Fenmerty 254-256). The article also
revealed that Merck revised dosing instructions in the
Fosamax product circular based on the results noted in the
Macon. The 4Amencan joumna of Gastroemerology. (1995) (PTX
a
87a
paper so as to further minimize potential for prolonged
contact of the drug with the esophagus and thus. to reduce the
risk of injury. (PTX 91 at 1020). Additional case reports
published by Abdelmalek (PTX 96), Sorrentino (PTX 9%),
Naylor (PTX 101), Rimmer (PTX 102), Pizzanni (PTX 109)
and Girelli (PTX 106) also suggested evidence that
alendronate sodium may be associated with severe side
effects not recognized in clinical trials. (Fennerty at 259).
The Court also finds that several studies dealing with
alendronate are significant. In 1993, Harris’ published an
early Phase II study, which is a dose-ranging study used to
determine the dose and the preliminary data on both the
safety and efficacy of a drug, sponsored by Merck in the
Journal of Clinical Endocrinology and Metabolism
investigating the effects of oral alendronate sodium
treatment. (PTX 116; Russell at 159, 364-65 ). The women in
this study were between the ages of 40 and 60 and did not
have osteoporosis. The women were treated with alendronate
sodium doses from 5 to 40 mg for six weeks and the dosages
were well-tolerated. (PTX 116 at 1399).
Merck then sponsored a study investigating the
effects of a range of different oral doses of alendronate for
the treatment of osteoporosis. (PTX 69). The results of this
study were published by Chestnut in 1995 in the American
Journal of Medicine. The Chestnut study lasted for two years
and involved 188 women with osteoporosis. (PTX 69: Yates
at 502-504). Of these women, 31 were exposed to placebo,
32 to 5 mg, 30 to 10 mg, 32 to 20 mg and 63 to 40 mg of
alendronate sodium. (PTX 69 at Table 1). As of 1996, the
Chestnut study was the only study that administered
alendronate sodium to osteoporosis patients. (PTX 69:
Harris, J f Clinical li (1993)
(PTX 116).
Markowitz at 478-479). Chestnut reported that nine women
discontinued alendronate sodium therapy due _ to
gastrointestinal side effects that included nausea, dyspepsia,
mild esophagitis/gastritis and abdominal pain. (PTX 69 at
150; Markowitz at 479-482; Fennerty at 265-66). Nine
women withdrew from treatment because of these side
effects: seven women withdrew from the 40 mg dose, one
woman withdrew from the 20 mg dose and one women
withdrew from the group taking between 5 and 10 mg doses.
(PTX 69 at 150; Markowitz at 479-482; Fennerty at 266;
Yates at 539-540). Chestnut also reported that the
gastrointestinal side effects “occurred primarily in the first
year during treatment with 40 mg alendronate.” (PTX 69 at
150, col. 1). Dr. Fennerty testified that the fact that 11.1% (7
out of 63) withdrew from the 40 mg alendronate dose was
noteworthy within the context of a clinical trial.*
Teva contends that the April and July 1996 editions of
the Lunar News render claims 29 and 37 of the '329 Patent
obvious. The July 1996 Lunar News issue contained a section
entitled, “Update Bisphosphonate.” (PTX 29 at 23). The
section discusses bisphosphonates as a treatment for
osteoporosis. Id. In reference to the use of alendronate for
treatment of osteoporosis, it states that “[s}ome United States
physicians are reluctant to treat because of: a) side effects; b)
difficulty of dosing; and (c) high costs ($700/year).” (PTX 19
* — The Court concludes that studies dealing with Paget's disease are not
relevant to its analysis because it was well-known to those of ordinary
skill in the art that patients with Paget's disease tolerate higher doses of
alendronate than patients with osteoporosis. (Papapoulos at 710-711; PTX
112 at 153; PTX 113 at 169; see also PTX 300 at 26). Thus, the Court
finds that tolerability of alendronate sodium from studies involving
Paget's patients should not be extrapolated to a discussion of osteoporosis
about the tolerability of alendronate. For this reason, the Court will not
address studies dealing with Paget's disease and the tolerability of higher
doses of alendronate sodium.
89a
at 23). To address the difficulty of dosing and high costs the
article suggested:
The difficulties with oral bisphosphonates may
favor their episodic (once/week) or cyclical (one
week each month) administration. Even oral
alendronate potentially could be given in a 40 or 80
mg dose once/week to avoid dosing problems and
reduce costs.
PTX 29 at 23. In a section entitled “Update:
Bisphosphonates,” the April 1996 edition of the Lunar News
discusses difficulties of the dosing regimen associated with
alendronate and states:
one of the difficulties with alendronate is its low
oral bioavailability. When taken with water in a
fasting state, only about 0.8% of the oral dose is
bioavailable. Even coffee or juice reduces this by
60%, and a meal reduces it by > 85%. Alendronate
must be taken, after an overnight fast, 30-60
minutes before breakfast. Subjects should remain
seated or standing; a very small group of patients
have reported some upper gastrointestinal distress if
this is not done. This regime may be difficult for the
elderly maintain chronically. An _ intermittent
treatment program (for example, once per week, or
one week every three months), with higher oral
dosing, needs to be tested.
DTX 417 at 31. (citations omitted).
iii. Differences Between the Prior Art
and the Claims at Issue
The Court concludes that the prior art cited above
demonstrates that the suggestion to give 40 or 80 mg of
90a
alendronate sodium to treat or prevent osteoporosis was not
clinically useful or obvious in July 1997 because of the
known dose-related gastrointestinal side effects. Further, the
Court is not persuaded that the two Lunar News articles, not
published in peer-reviewed journals or authered by one
skilled in the art, either alone or in combination, overcame
the serious side effect concerns associated with higher dosage
units of alendronate sodium. For example, Dr. Fennerty,
whom the Court finds very credible, testified that in light of
the prior art, any physician would have been “extraordinarily
concerned” to suggest a 40 or 80 mg dose because
alendronate sodium was a new compound that had been
associated with dose-related injury and severe injuries in case
reports. (Fennerty at 270-271; see also PTX 69, 91, PTX 300
at 14). In this regard Dr. Fennerty testified:
Q: Now in July of '97 or any period preceding that,
what would your opinion be about a suggestion that
you give 40 or 80 milligrams of alendronate to an
osteoporotic woman?
A. Given what I just described, a new compound, a
Dear [D]octor letter, publications in the New
England Journal of severe caustic injury, smattering
case reports around that, the Chestnut [sic] paper
before talking about as you go up on a dose, that
you may be seeing more adverse effects, the
smattering of papers, and now animal data showing
that types of patients that use NSAIDS use some
higher dose of these compounds, shows evidence of
gastric injury in the model, I would have been
extraordinarily concerned about anybody suggesting
that this was a useful clinical approach at that point
and time.
(Fennerty at 270-21). Additionally, Dr. Papapoulous testified
about the concerns of side effects associated with the
9la
suggestion in the July 1996 Lunar News where he stated,
“{Lunar News] is using 40 and 80 not on any scientific
rationale, but because it is available. Secondly, he doesn't tell
us how he's going to address the issue of side effects, which
is one of the main points in this particular article.”
Papapoulos at 665-666. Thus, in light of the case reports, and
the Chestnut study, in conjunction with observations written
about alendronate by Dr. Fleish, the Court concludes that the
Lunar News references did not render the seven-fold daily
dose of alendronate for the treatment and prevention of
osteoporosis obvious given the clearly documented and
known dose related gastrointestinal side effects associated
with high doses (over 20 mg) of oral alendronate.
First, the April 1997 Lunar News did not deal with
the specific dosages of 70 or 35 mg in relation to its
discussion of once-weekly dosing of alendronate. Second, the
July 1996 Lunar News listed 40 and 80 as compared to 70
and 35 mg dosages as suggested by the '329 Patent and did
not deal with the problem of known gastrointestinal side
effects. Additionally, in reaching its conclusion, the Court
gives more weight to the prior art references written and
reviewed by those skilled in the art such as the Chestnut
study and the De Groen case report as opposed to the Lunar
News, a quarterly newsletter written by someone without a
Ph.D. or MD. in the applicable field.
iv. Secondary _Indicia of Non-
Obviousness .
As for the secondary considerations of non-
obviousness, the Court finds that Merck has presented
sufficient evidence to show that the 35 mg and 70 mg once-
weekly dosing of Fosamax was commercially successful. On
this issue, the Court finds Dr. Vellturo's testimony persuasive.
92a
Dr. Vellturo testified regarding the evidence of increased
sales after the launch of once-weekly Fosamax.
Originally, Merck's Fosamax osteoporosis product
line consisted of once-daily 10 and 5 mg Fosamax tablets.
(D.1. 138 at 32). Dr. Vellturo testified that daily Fosamax was
a successful product that enjoyed an average increase in sales
of 152 million dollars per year for each of the four years
preceding the introduction of the once-weekly Fosamax.
(Vellturo at 718-720; PTX 166; PTX 300 at 37). In 2001, the
first full year following the launch of the once-weekly dosing
regimen, the sales increase was 343 million dollars, more
than double the expected increase, without any corresponding
relative increase in expenditures. (Vellturo at 719-720; PTX
166; PTX 300 at 37).
The Court finds that further evidence of the success
of the once-weekly dosing regimen is present in the
prescription data for the Fosamax tablets. A sharp increase in
physician adoption of Fosamax upon the introduction of the
once-weekly dosing regimen is manifested in the number of
total prescriptions reported each month for Fosamax.
(Vellturo at 723; PTX 164; PTX 300 at 32, 33, 36). The
marked increase in prescription volume of once weekly
dosages of Fosamax tablets is more compelling in light of its
effects on the osteoporosis market in general. FAME is an
acronym for the four prescription drug products whose
primary indication is for the treatment of osteoporosis, (i.c¢.,
Fosamax, Actonel, Miacalcin, and Evista). (Vellturo at 722,
753-754). IMS is a data collection firm specializing in data
reflecting the prescribing patterns of physicians and in
prescription volume data. (Vellturo at 716-717). Within six
months of its launch, once-weekly Fosamax tabiets became
the most prescribed drug in the FAME market. (PTX 164;
PTX 165; PTX 300 at 33). Based on the IMS data points
present in the plot of monthly total prescriptions, it can be
93a
calculated that the Fosamax franchise share of the FAME
market grew from 45 % to 55 % in the first six months after
the introduction of the once-weekly dosing regimen. (PTX
164; PTX 300 at 33).
Teva's expert Dr. Rozek testified that the increase in
Fosamax sales could be due to other factors such as the
increasing number of Americans over the age of sixty, the
increasing awareness of osteoporosis, an increase in the
number of people seeking treatment for osteoporosis and
Merck's marketing efforts. However, the Court finds Dr.
Rozek's explanation unpersuasive because he offered no
affirmative opinion as to what affect these factors would have
on the analysis of the FAME market as a whole or with
Fosamax individually. (Rozek at 871-72; 869; 878). In fact,
Dr. Rozek testified the he was “not instructed to do anything
affirmative with regard to the meaw...ng of any relationship
that might exist between the ['32% Patent] and sales, or
success of Fosamax.” (Rozek at 869). In the Court's view, Dr.
Rozek's suggestion that there are factors that Dr. Vellturo
should have considered, is not sufficient to rebut the
affirmative evidence of the commercial success of the once-
weekly dosing regimen. (Rozek at 878-79). Also, the Court
concludes that Merck has shown a sufficient nexus between
the claimed secondary considerations and the patented
method given the testimony of Dr. Vellturo and the timing of
the launch of the once-weekly dosing regimen for Fosamax.
Accordingly, the Court has given the above discussed
secondary considerations the importance they deserve in
reaching its conclusion of nonobviousness. See Minnesota
Orthopedics, Inc. 976 F.2d 1559, 1573 (Fed. Cir. 1992)
(noting the importance of secondary considerations in the
obviousness analysis).
94a
v. Summary
In sum, the Court concludes that Teva has not proven
by clear and convincing evidence that it was obvious to
combine the Lunar News suggestions in light of the
knowledge of one of ordinary skill in the art of the
gastrointestinal side effects accompanying large doses of oral
alendronate. In addition, the Court finds that the significant
secondary considerations offered by Merck undermine any
claim of obviousness, and accordingly, the Court concludes
that Teva has not proven by clear and convincing evidence
that the ‘329 Patent was obvious in light of prior art.
V Unenforceability Due To Inequitable Conduct
A The Inequitable Conduct Standard
As a general matter. patent applicants and their patent
attorneys have a duty of candor. good faith and honesty in
their dealings with the PTO. 37 C.F.R. § 1.56(a). The duty of
candor. good faith and honesty includes the duty to submit
truthful information and the duty to disclose to the PTO
information known to the patent applicants or their attorneys
which is material to the examination of the patent
application. Elk Corp. of Dallas v. GAF Bldg. Materials
Corp.. 168 F. 3d 28. 30 (Fed. Cir. 1999). Breach of the duty
of candor. good faith and honesty may constitute inequitable
conduct id. If it is established that a patent applicant engaged
in inequitable conduct before the PTO, the entire patent
application so procured is rendered unenforceable.
Kingsdown Medical Consultants _v. Hollister Incorporated,
&63 F.2d 867. 877 (Fed. Cir. 1988).
A patent applicant engages in inequitable conduct
before the PTO when he withholds or misrepresents
information materia] to the patentability of his invention,
with an intent to deceive.
95a
See Nobelpharma AB v. Implant Innovations. Inc..
141 F.3d 1059, 1064 (Fed. Cir. 1998); (citing Molins PLC v.
dextron. Inc., 48 F.3d 1172, 1178 (Fed. Cir. 1995)).
Inequitable conduct cncompasses affirmative
misrepresentations of material fact, failure to disclose
material information, or submission of false material
information, coupled with an intent to deceive. Baxter Int'l,
Inc. v. McGaw Inc., 149 F.3d 1321, 1327 (Fed. Cir. 1998)
(citing Nobelpharma, 141 F.3d at 1068-71). In order to
establish unenforceability based on inequitable conduct, Teva
must prove, by clear and convincing evidence, that material
information was intentionally withheld for the purpose of
misleading or deceiving the patent examiner. See Allied
Colloids _v. Ameri id Co., 64 F.3d 1570,
1578 (Fed. Cir. 1995) (citation omitted).
A determination of inequitable conduct entails a t
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