SZEGEDI TUDOMÁNYEGYETEM

Patent Trials and Appeals Board

Jun 15, 2020

2019005815 (P.T.A.B. Jun. 15, 2020)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
14/407,498 12/12/2014 András Varró DAN-134 8124
12495 7590 06/15/2020
Jason D. Voight
3312 N. Kensington St.
Arlington, VA 22207
EXAMINER
RAMACHANDRAN, UMAMAHESWARI
ART UNIT PAPER NUMBER
1627
NOTIFICATION DATE DELIVERY MODE
06/15/2020 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
jason.voight@gmail.com
jason.voight@voightip.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte ANDRÁS VARRÓ, PÉTER MÁTYUS,
ISTVÁN BACZKÓ, GYÖRGY FALKAY, NORBERT JOST,
ISTVÁN LEPRÁN, ANITA SZTOJKOV-IVANOV,
LÁSZLÓ VIRÁG, and NORBERT BUZÁS
__________

Appeal 2019-005815
Application 14/407,498
Technology Center 1600
__________

Before FRANCISCO C. PRATS, ELIZABETH A. LAVIER, and
RACHEL H. TOWNSEND, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL

Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 5–11. We have jurisdiction under
35 U.S.C. § 6(b).
We AFFIRM.

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant states that the real party in interest Szegedi
Tudományegyetem. Appeal Br. 2.
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STATEMENT OF THE CASE
The following rejections are before us for review:
(1) Claims 5–11 under 35 U.S.C. § 103(a) as being unpatentable over
Varro 1,2 Varro 2,3 Tieleman,4 and Letelier5 (Ans. 4–8);
(2) Claims 5–9 under 35 U.S.C. § 103(a) as being unpatentable over
Tieleman, Letelier, and Varro 2 (Ans. 8–10); and
(3) Claims 5–9 under 35 U.S.C. § 103(a) as being unpatentable over
Tieleman, Letelier, Nattel,6 and Varro 2 (Ans. 10–13).
Appellant’s claim 5, the sole independent claim on appeal, is
representative and reads as follows:
5. A method for the treatment and/or reducing the
incidence of atrial fibrillation, said method comprising orally
administering to a human or animal a pharmaceutical
composition comprising a compound selected from the group
consisting of desethylamiodarone [(DEA)] and
pharmaceutically acceptable salts, hydrates and solvates
thereof, together with pharmaceutically acceptable excipients,
vehicle and/or carrier.

2 András Varró et al., Antiarrhythmic effect of desethylamiodarone in
conscious rats, 39 J. PHARM. PHARMACOL. 483–484 (1987).
3 A. Varro et al., Long-term cardiac electrophysiological effect of
desethylamiodarone in dog cardiac muscle, 22 EUR. HEART J. 55 (Abstr.
Suppl., abstract P415) (2001).
4 Robert G. Tieleman et al., Efficacy, Safety, and Determinants of
Conversion of Atrial Fibrillation and Flutter With Oral Amiodarone, 79
AMERICAN J. CARDIOL. 53–57 (1997).
5 Luz M. Letelier et al., Effectiveness of Amiodarone for Conversion of
Atrial Fibrillation to Sinus Rhythm, 163 ARCH. INTERN. MED. 777–785
(2003).
6 Stanley Nattel et al., The antiarrhythmic efficacy of amiodarone and
desethylamiodarone, alone and in combination, in dogs with acute
myocardial infarction, 77 CIRCULATION 200–208 (1988).
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Appeal Br. 15.
OBVIOUSNESS—
VARRO 1, VARRO 2, TIELEMAN, AND LETELIER
The Examiner’s Prima Facie Case
In rejecting Appellant’s claims 5–11 over Varro 1, Varro 2, Tieleman,
and Letelier, the Examiner cited Varro 1 and Varro 2 as evidence that
desethylamiodarone (DEA) was known in the art to be useful for treating
cardiac arrhythmias. Ans. 5–6. In particular, the Examiner noted the
teaching in Varro 1 that DEA is a metabolite of amiodarone (AMIO) that
appears in plasma and accumulates in cardiac muscle during chronic
treatment of cardiac arrhythmias with AMIO. Id. at 5. The Examiner also
specifically noted Varro 1’s teaching that the electrophysiological effects of
DEA are very similar to the effects of AMIO. Id.
In Varro 2, the Examiner noted the teaching of “the possibility that
DEA treatment alone would be effective and may be a less dangerous
antiarrhythmic treatment than that of AMIO (see P 415).” Ans. 6.
The Examiner conceded that Varro 1 and Varro 2 differ from the
rejected claims in that “Varro 1 explicitly demonstrate[s] the anti-arrhythmic
activity of DEA but do[es] not teach the arrhythmia to be treated as atrial
fibrillation.” Ans. 6.
As evidence that it would have been obvious to orally administer
DEA to treat atrial fibrillation as recited in Appellant’s claims, the Examiner
cited Tieleman as disclosing that, when chronically administering AMIO to
treat atrial fibrillation, plasma levels of the metabolite DEA were more
important than levels of the parent compound, AMIO. Ans. 7. The
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Examiner cited Letelier as evidence that AMIO was known to be useful for
treating atrial fibrillation in an oral dosage regimen. Id.
Based on the references’ combined teachings, the Examiner
concluded that it would have been obvious to orally administer DEA to treat
atrial fibrillation. See Ans. 7–8.
Analysis
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992)
(citations omitted):
[T]he examiner bears the initial burden . . . of presenting a
prima facie case of unpatentability. . . .
After evidence or argument is submitted by the applicant in
response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.
Having carefully considered all of the arguments and evidence
advanced by Appellant and the Examiner, Appellant does not persuade us
that a preponderance of the evidence fails to support the Examiner’s
conclusion of obviousness as to Appellant’s representative claim 5.
As seen above, representative claim 5 recites treating and/or reducing
the incidence of atrial fibrillation by orally administering a pharmaceutical
composition that contains DEA, or pharmaceutically acceptable salts,
hydrates, and solvates thereof, together with a pharmaceutically acceptable
excipient, vehicle, and/or carrier. Appeal Br. 15.
As explained in Letelier, atrial fibrillation is “the most commonly
encountered arrhythmia.” Letelier 777. Letelier discloses, moreover, that
AMIO “is effective for converting AF [(atrial fibrillation)] to sinus rhythm
in a wide range of patients.” Id.
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Tieleman, similar to Letelier, discloses that chronic oral
administration of AMIO is an effective treatment for atrial fibrillation. See
Tieleman 53 (“[AMIO] loading is safe and is still able to convert refractory
atrial fibrillation or flutter.”) (Abstract).
Although neither Letelier nor Tieleman discloses treating atrial
fibrillation patients with DEA as recited in Appellant’s claim 5, Tieleman
discloses that the therapeutic antiarrhythmic effects of chronic oral
administration of AMIO are positively correlated with plasma levels of
DEA, the metabolite of AMIO. See Tieleman 53 (“Conversion is related to
increased [DEA] plasma levels and concomitant treatment with verapamil.
Because prolonged loading may increase [DEA] plasma concentrations, this
may enhance efficacy and obviate the need for electrical cardioversion.”);
see also id. at 56 (“The present study showed that for conversion of atrial
fibrillation, plasma concentrations of [DEA] were more important than those
of the parent compound.”).
Given Tieleman’s determination that, when treating atrial fibrillation
by chronic oral administration of AMIO, the plasma concentration of DEA
was more important to the therapeutic effect than the plasma concentration
of AMIO, we agree with the Examiner that a skilled artisan had a good
reason for administering DEA, instead of AMIO, when treating atrial
fibrillation. The teachings in Varro 1 and Varro 2 bolster that finding.
Specifically, turning first to Varro 2, the reference describes a study of
chronic oral administration of DEA to dogs and, based on the results of the
study, “[i]t was concluded that chronic DEA treatment exerts
electrophysiological changes similar to those seen after long-term AMI[O]
treatment.” Varro 2 at 55. Varro 2 states that its conclusion “further argues
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for the important role of the metabolite during chronic AMI[O]
administration, and raises the possibility that DEA treatment alone would be
an effective and may be a less dangerous antiarrhythmic treatment than that
of AMI[O].” Id.
Given Varro 2’s teaching that chronic oral administration of DEA
exerts therapeutic antiarrhythmic effects similar to those of AMIO, as well
as its teaching that DEA treatment would possibly be an effective and less
dangerous antiarrhythmic treatment than AMIO, we agree with the
Examiner that a skilled artisan, viewing Varro 2 alongside the teachings
discussed above in Tieleman and Letelier, had a good reason for, and a
reasonable expectation of success in, chronic oral administration of DEA,
instead of AMIO, as a treatment for atrial fibrillation (the most commonly
encountered arrhythmia).
The obviousness of oral administration of DEA to treat atrial
fibrillation, including chronic administration of the drug, is further bolstered
by the teachings of Varro 1. Varro 1 discloses a study of the effects of
intraperitoneal administration of DEA to rats having experimentally induced
arrhythmias, among them ventricular fibrillation. See Varro 1 at 483–484.
Varro 1 discloses that its study was prompted by previous
investigations finding that chronic AMIO administration results in the
appearance of DEA in plasma and accumulation of DEA in cardiac muscle.
Varro 1 at 483. Varro 1 also notes that previous “[e]lectrophysiological
studies indicate that [DEA] delayed repolarization of cardiac muscle both in-
situ and in-vitro.” Id. (citations omitted). Based on those previous
investigations, Varro 1 hypothesized that “it is likely that the effects of
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[DEA] contribute to the strong antiarrhythmic efficacy of the chronic
[AMIO] administration.” Id.
To confirm its hypothesis that DEA contributes to the strong
antiarrhythmic effect of chronic AMIO administration, Varro 1 pretreated
rats with DEA, then induced arrhythmias (including ventricular fibrillation)
in the rats by ligating a coronary artery, and examined the results. See
Varro 1 at 483–484. Varro 1 discloses that its results “show that DEA
pretreatment improved the survival in the acute phase of arrhythmias caused
by coronary ligation in conscious rats” and that the “antiarrhythmic effects
were produced by a dose of [DEA] comparable with that of [AMIO] we
have already reported to be effective in the present model.” Id. at 484
(citation omitted). Based on the results of its experiments, Varro 1
concluded that “[a]lthough the antiarrhythmic effect of [DEA] needs to be
examined in other species, including man, we assume that it contributes to
the antiarrhythmic effect seen after chronic [AMIO] administration.” Id. at
484.
Given Varro 1’s teaching that DEA contributes to the antiarrhythmic
effect seen after chronic AMIO administration, as well as its teaching that
DEA exerts electrophysiological effects similar to the effects of AMIO, we
agree with the Examiner that a skilled artisan, viewing Varro 1 alongside the
teachings discussed above in Varro 2, Tieleman, and Letelier, had a good
reason for, and a reasonable expectation of success in, chronic oral
administration of DEA, instead of AMIO, as a treatment for atrial fibrillation
(the most commonly encountered arrhythmia). Accordingly, for the reasons
discussed, we agree with the Examiner that the process recited in
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Appellant’s representative claim 5 would have been prima facie obvious to a
skilled artisan.
Appellant’s arguments do not persuade us to the contrary. We
acknowledge, as Appellant contends, that none of the cited references
expressly describes treating atrial fibrillation by orally administering DEA.
See Appeal Br. 5–6. We also acknowledge Appellant’s contention that
“[t]he prior art does not provide any indication or suggestion that DEA has
the role of treatment of atrial fibrillation or can be used as the medicament
for the treatment of atrial fibrillation.” Id. at 7.
As discussed above, however, both Varro 1 and Varro 2 teach that
DEA is as effective as AMIO for treating arrhythmias, including by chronic
oral administration, and DEA exerts similar electrophysiological effects on
the heart as AMIO. As also discussed above, Varro 2 in particular expressly
suggests that “DEA treatment alone would be an effective and may be a less
dangerous antiarrhythmic treatment than that of AMI[O].” Varro 2 at 55.
And, as also discussed above, Tieleman teaches that when treating atrial
fibrillation with chronically administered oral AMIO, the plasma
concentrations of DEA are more important to the therapeutic effect than the
plasma concentrations of AMIO. See Tieleman 56. Appellant does not
persuade us, therefore, that a skilled artisan treating atrial fibrillation by
chronic oral administration of AMIO as taught for example in Tieleman and
Letelier, lacked a good reason for, or a reasonable expectation of success in,
chronically administering oral DEA, instead of AMIO.
We acknowledge Appellant’s contention that a skilled artisan, absent
evidence to the contrary, might hypothetically expect that not all metabolites
would be as useful as their parent compound. See Appeal Br. 7. However,
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given the express teachings in Tieleman, Varro 1, and Varro 2 as to the
therapeutic effect of DEA, we are not persuaded that a skilled artisan lacked
a reasonable expectation that chronic oral administration of DEA would
treat atrial fibrillation. See In re Kubin, 561 F.3d 1351, 1360 (Fed. Cir.
2009) (“Obviousness does not require absolute predictability of success. . . .
For obviousness under § 103, all that is required is a reasonable expectation
of success.”) (quoting In re O’Farrell, 853 F.2d 894, 903–04 (Fed. Cir.
1988) (emphasis removed)).
We are not persuaded, moreover, that the Nattel reference would have
undermined the reasonable expectation of success provided by the
combination of references discussed above, nor are we persuaded that Nattel
teaches away from treating atrial fibrillation by chronic oral administration
of DEA. See Appeal Br. 7–8.
Nattel describes a study of the effects of intravenous administration of
both AMIO and DEA to dogs having experimentally induced ventricular
arrhythmias. See Nattel 200–201.
Nattel notes that “[p]lasma and myocardial drug concentrations were
similar to those measured during long-term [AMIO] therapy in man.” Nattel
200 (abstract); see also id. at 207 (“The plasma and myocardial drug
concentrations achieved in our dogs were in the same range as
concentrations occurring with long-term oral [AMIO] treatment.”).
Nattel discloses that “[b]oth [AMIO] and [DEA] suppressed
ventricular arrhythmias in a dose-dependent fashion. The metabolite
[(DEA)], however, was more potent with a 50% effective concentration for
suppression of premature ventricular complexes of 1.4 mg/liter compared
with 4.6 mg/liter for the parent compound.” Nattel 200 (abstract); see also
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id. at 207 (“In our experiments, the antiarrhythmic potency of [DEA] was
about three times that of [AMIO] based on plasma concentration.”).
Nattel concluded that its experiments “suggest that the accumulation
of [DEA] that occurs with long-term oral [AMIO] therapy contributes
importantly to the antiarrhythmic effects of the drug, and may account for
the gradual increase in antiarrhythmic action during the course of [AMIO]
therapy.” Nattel 200 (abstract).
Nattel, thus, teaches that DEA accumulation is important to the
therapeutic antiarrhythmic effect of chronic AMIO treatment, and that DEA
can exert a more potent effect than AMIO. Accordingly, rather than
teaching away from the claimed invention, Nattel bolsters the suggestion
from the collective teachings of Varro 1, Varro 2, Tieleman, and Letelier
discussed above that chronic oral administration of DEA would be a suitable
treatment for atrial fibrillation.
Appellant contends that the following discussion in Nattel teaches
away from orally administering DEA to treat atrial fibrillation (Appeal Br.
8):
Extrapolation of the results of intravenous drug
administration in dogs to the effects of long-term oral drug
therapy in man requires great caution. The plasma and
myocardial drug concentrations achieved in our dogs were in
the same range as concentrations occurring with long-term oral
amiodarone treatment. Single-dose intravenous [AMIO] is
known to be much more effective against supraventricular
than ventricular arrhythmias. This may be due to the greater
effect of [AMIO] compared with its metabolite [(DEA)] on
slow-channel function.
Nattel 207 (emphasis added).
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The passage in Nattel cited by Appellant, however, does not criticize,
discredit, or even specifically discuss whether oral administration of DEA
would be expected to be useful for treating atrial fibrillation. Appellant does
not persuade us, therefore, that the quoted language in Nattel is sufficient to
teach away from the claimed invention. See DePuy Spine, Inc. v. Medtronic
Sofamor Danek, Inc., 567 F.3d 1314, 1327 (Fed. Cir. 2009) (A reference
“does not teach away . . . if it merely expresses a general preference for an
alternative invention but does not criticize, discredit, or otherwise discourage
investigation into the invention claimed.”) (internal quotations omitted)
(citation omitted).
Appellant, moreover, fails to explain specifically how or why Nattel’s
teaching regarding single dose AMIO administration, or AMIO’s greater
effect on slow-channel function as compared to DEA, would have
discouraged investigation into treating atrial fibrillation by chronic oral
administration of DEA, as suggested by the teachings of Varro 1, Varro 2,
Tieleman, and Letelier discussed above. If anything, Nattel’s teaching that
AMIO exerts more potent effects against supraventricular (i.e., atrial)
arrhythmias bolsters the suggestion from Tieleman, Varro 1, and Varro 2
that DEA, having similar therapeutic effects to AMIO, would also be
effective against supraventricular arrhythmias such as atrial fibrillation.
In sum, for the reasons discussed, Appellant does not persuade us that
the Examiner erred in determining that the process recited in Appellant’s
representative claim 5 would have prima facie obvious to a skilled artisan.
Appellant does not persuade us, moreover, that it has advanced
objective evidence of nonobviousness sufficient to outweigh the prior art
evidence of prima facie obviousness advanced by the Examiner. In
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particular, we are not persuaded that Appellant’s evidence as to long-felt
need is entitled to significant probative weight. See Appeal Br. 10 (citing
Varro Decl.);7 Reply Br. 1–2.
Appellant “emphasizes that there has been a long-felt need not just for
a treatment of AF [(atrial fibrillation)], but for a better treatment of AF with
fewer adverse side-effects than exhibited by [AMIO] (see, e.g., specification
page 1, lines 12-14, 31).” Appeal Br. 10.
We acknowledge the Specification’s disclosure that “AMIO — which
has a very complex mode of action inhibiting cardiac sodium, calcium,
potassium currents and beta adrenoceptors — also exerts serious
extracardiac adverse effects like pulmonary fibrosis, hepatotoxicity,
photodermatosis, cornea deposits etc. which greatly limit its clinical use
(Tisdale et al, 1995).” Spec. 1.
Establishing long-felt need, however, “requires objective evidence
that an art-recognized problem existed in the art for a long period of time
without solution.” Ex parte Jellá, 90 USPQ2d 1009, 1019 (BPAI 2008)
(precedential; emphasis added); see also Graham v. John Deere Co., 383
U.S. 1, 17–18 (1966) (secondary considerations include “long felt but
unsolved needs”) (emphasis added).
The fact that it may have been known for a long time that AMIO
treatment of atrial fibrillation had significant side effects does not establish
that the need for a lower side effect atrial fibrillation treatment was
unsolved. In that regard, we are not persuaded that Appellant has shown

7 Declaration of Dr. Andras Varró under 37 C.F.R. § 1.132 (signed February
21, 2017).
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sufficiently that effective treatments for atrial fibrillation having little or few
side effects, or at least fewer than AMIO, were not available in the prior art.
We acknowledge the Varro Declaration’s assertion that “many have
sought to find a treatment with fewer or less severe adverse side effects”
than AMIO, as evidenced by an “enclosed [] list of hundreds of published
research articles wherein effects of AMIO such as thyroid dysfunction,
pulmonary toxicity; hepatocellular toxicity, liver injury and drug-drug
interactions have been studied and reported.” Varro Decl. ¶ 3.
The Varro Declaration, however, includes no specific discussion of
any of the articles in the cited list. Nor does the Varro Declaration include
any specific explanation as to how or why any of the articles in the cited list
establishes that the prior art had failed to solve the need for a reduced side
effect treatment for atrial fibrillation. Absent some specific evidence-based
explanation as to why the articles in the list cited in the Varro Declaration
support the assertions made in the declaration, we are not persuaded that the
conclusory assertions in the declaration are sufficient to establish that the
asserted need was unsolved, or that significant efforts had failed to solve the
problem. See In re Allen, 324 F.2d 993, 997 (CCPA 1963) (An allegation of
a long felt but unsolved problem in the art “is not evidence of unobviousness
unless it is shown . . . that the widespread efforts of skilled workers having
knowledge of the prior art had failed to find a solution to the problem.”).
In sum, for the reasons discussed, we find that Appellant’s evidence
as to long-felt but unsolved need is not entitled to significant probative
weight. Similarly, we find that Appellant’s evidence of unexpected results is
not sufficient to outweigh the prior art evidence of obviousness advanced by
the Examiner.
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Appellant contends that “Examples 1 to 4 of the present
application . . . demonstrate that oral administration of DEA has
unexpectedly higher therapeutic efficacy than oral administration of
amiodarone, and unexpectedly lower toxic side effect to the liver, lung and
other tissues of patients.” Appeal Br. 11. Regarding unexpected results, the
Varro Declaration states as follows:
[C]ontrary to the prior art disclosures, the data of the
present application establishes for the first time that in addition
to being significantly more effective, DEA shows markedly
decreased side effects when administered daily. In fact, half the
dose of DEA needs to be administered relative to AMIO to
achieve the same clinical effects. These effects are accompanied
by similar cardiac tissue DEA levels, i.e. the bioavailability of
DEA is also superior. Therefore more importantly,
administration of DEA lead to reduced pathological alterations in
the lungs and the liver, i.e. similar antiarrhythmic effects are
accompanied with milder toxic and adverse effects. In my
opinion, such results of the present invention would not have
been expected without performing the experiments described in
our patent application based on the view of the references cited
in the aforementioned Office action [of November 21, 2016].
Varro Decl. ¶ 3.
While Appellant asserts that Example 1 in the Specification shows
unexpected results, neither Appellant’s briefs nor the Varro Declaration
include any specific analysis of Example 1, or any specific discussion why
Example 1 is evidence of unexpected results. In any event, Appellant’s
Example 1 involves analysis of excised rabbit hearts in which atrial
fibrillation was induced by electrical stimulation. See Spec. 8–9. The
Specification states that the results of the experiments in Example 1 “suggest
that DEA may be a promising drug candidate for treatment and/or
prevention of atrial fibrillation.” Id. at 9.
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As discussed above, however, Tieleman, Varro 1, and Varro 2 all
disclose that DEA has antiarrhythmic properties similar to AMIO, a drug
known in the art to treat atrial fibrillation. Thus, even putting aside the
speculative nature of the Specification’s conclusion as to the results of
Example 1, we are not persuaded that the results in Example 1 would have
been unexpected.
While Appellant asserts that Example 2 in the Specification shows
unexpected results, neither Appellant’s briefs nor the Varro Declaration
include any specific analysis of Example 2, or any specific discussion why
Example 2 is evidence of unexpected results. In any event, Appellant’s
Example 2 analyzes the effect in conscious rats of one month pretreatment
with either DEA or AMIO, followed by a surgically induced myocardial
infarction. See Spec. 10–11. As to the results of the experiments in
Example 2, the Specification states as follows:
Long-term oral AMIO or DEA pretreatment provided
significant protection against life threatening arrhythmias and
improved the chance to survive the acute phase of experimental
myocardial infarction. This protective effect was produced by
similar plasma or myocardial DEA concentrations. However,
this effective concentration could be achieved by applying
smaller doses of DEA.
Spec. 11 (emphasis added).
We first note that Example 2 makes no specific mention of atrial
fibrillation, the disorder treated in Appellant’s representative claim 5. We
note, moreover, that the effect seen in Example 2 came from chronic
administration of DEA, whereas representative claim 5 is not limited to
chronic administration. We are not persuaded, therefore, the results shown
in Example 2 are commensurate in scope with claim 5.
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As to the fact that DEA was shown to be more potent than AMIO in
Appellant’s Example 2, we note Nattel’s disclosure that DEA was seen to be
more potent than AMIO in similar experiments performed on dogs. See
Nattel 200 (disclosing that DEA “was more potent with a 50% effective
concentration” as compared to AMIO); see also id. at 207 (“In our
experiments, the antiarrhythmic potency of [DEA] was about three times
that of [AMIO] based on plasma concentration.”). Given these disclosures
in Nattel, we are not persuaded that Appellant has explained sufficiently
why the results of Appellant’s Example 2 would have been considered
unexpected.
Appellant’s Example 3 analyzes the effects of four weeks of chronic
oral treatments with either DEA or AMIO on pacemaker-induced atrial
fibrillation in dogs. See Spec. 11–16.
As to the results of the experiments in Example 3, the Specification
states that “chronic oral [AMIO] (50 mg/kg/day) and [DEA] (25 mg/kg/day)
treatment effectively and similarly decreased the incidence of atrial
fibrillation, the duration of atrial fibrillation episodes and increased atrial
effective refractory periods in conscious, chronically instrumented Beagle
dogs.” Id. at 14. As to Example 3, the Specification also notes that “liver
and lung tissue DEA levels were significantly and markedly higher
following AMIO treatment than following DEA treatment.” Id.
Example 3 thus shows that in a dog model of atrial fibrillation, orally
administered DEA exerts similar therapeutic effects at half the dosage of
AMIO, consistent with Appellant’s arguments. See Appeal Br. 10–12;
Varro Decl. ¶ 3. As noted above, however, Nattel discloses that DEA was
seen to have significantly more potent antiarrhythmic properties than AMIO
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in dog experiments. See Nattel 200, 207. Although Nattel did not disclose
that its experiments involved atrial fibrillation, Nattel’s results nonetheless
suggest that the superior potency of DEA seen in Appellant’s Example 3
was not unexpected. Given Nattel’s disclosure, we are not persuaded that
Appellant has explained sufficiently why the results of Appellant’s Example
3 would have been considered unexpected.
The results seen in Example 3, moreover, came from chronic
administration of DEA, whereas representative claim 5 is not limited to
chronic administration. We note, moreover, that claim 5 does not include
any limitations as to dosage, and therefore encompasses dosages that would
be expected to be effective for AMIO. We are not persuaded, therefore, that
the results shown in Example 3 are commensurate in scope with claim 5, or
that claim 5 reflects the asserted unexpected improvement in DEA dosage as
compared to AMIO.
While Appellant asserts that Example 4 in the Specification shows
unexpected results, neither Appellant’s briefs nor the Varro Declaration
include any specific analysis of Example 4, or any specific discussion why
Example 4 is evidence of unexpected results. In any event, Appellant’s
Example 4 is a 28-day toxicology study in rats that received either 200
mg/kg/day of AMIO or 100 mg/kg/day of DEA. See Spec. 16–17. As to
liver toxicity, the Specification states that the results of the experiments in
Example 4 “may suggest that treatment with the metabolite (DEA) leads to
reduced hepatotoxic side effects compared to treatment with amiodarone
(AMIO).” Id. at 17. As to lung toxicity, the Specification states that the
results of the experiments in Example 4 “may suggest that DEA treatment
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might be more beneficial considering one of the most serious adverse effects
of chronic AMIO treatment, the development of pulmonary fibrosis.” Id.
The results seen in Example 4, however, came from chronic
administration of DEA, whereas representative claim 5 is not limited to
chronic administration. We note again, moreover, that claim 5 does not
include any limitations as to dosage, and therefore encompasses higher DEA
dosages than tested in Example 4. We are not persuaded, therefore, that the
results shown in Example 4 are commensurate in scope with claim 5, or that
claim 5 reflects the asserted unexpected improvement in DEA dosage as
compared to AMIO. Moreover, given that the DEA dosage was half the
AMIO dosage, we are not persuaded that Appellant has explained
sufficiently why the results of Appellant’s Example 4 would have been
considered unexpected.
In sum, for the reasons discussed, Appellant does not persuade us that
the Examiner erred in determining that the process recited in Appellant’s
representative claim 5 would have prima facie obvious to a skilled artisan.
For the reasons discussed, Appellant also does not persuade us that it has
advanced objective evidence of nonobviousness sufficient to outweigh the
prior art evidence of prima facie obviousness advanced by the Examiner.
We note in particular that where, as here, the prior art presents a strong case
of obviousness, secondary considerations “do not necessarily control the
obviousness conclusion.” Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1372
(Fed. Cir. 2007) (citation omitted).
In sum, for the reasons discussed, based on the totality of the record,
we find that the preponderance of the evidence supports the Examiner’s
conclusion that the process of representative claim 5 would have been
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obvious in view of Varro 1, Varro 2, Tieleman, and Letelier. We therefore
affirm the Examiner’s rejection of claim 5 over those references. Claims 6–
11 fall with claim 5. See 37 C.F.R. 41.37(c)(1)(iv).
OBVIOUSNESS—
TIELEMAN, LETELIER, AND VARRO 2
In rejecting Appellant’s claims 5–9 over Tieleman, Letelier, and
Varro 2, the Examiner relied on substantially the same teachings in each of
the references discussed above, except for Varro 1. See Ans. 8–10.
As discussed above, given Varro 2’s teaching that chronic oral
administration of DEA exerts therapeutic antiarrhythmic effects similar to
those of AMIO, as well as its teaching that DEA treatment would possibly
be an effective and less dangerous antiarrhythmic treatment than AMIO, we
agree with the Examiner that a skilled artisan, viewing Varro 2 alongside the
teachings discussed above in Tieleman and Letelier, had a good reason for,
and a reasonable expectation of success in, chronic oral administration of
DEA, instead of AMIO, as a treatment for atrial fibrillation (the most
commonly encountered arrhythmia).
In traversing this rejection, Appellant states only that it “hereby fully
incorporates by reference the above comments regarding the rejection of
Claims 5–11 under 35 U.S.C. 103(a) as being unpatentable over Varro I and
Varro 2 in view of Tieleman et al. and Letelier et al., which comments are
believed to fully address this rejection.” Appeal Br. 12.
As discussed above, we do not find those arguments persuasive. We
therefore affirm the Examiner’s rejection of claims 5–9 over Tieleman,
Letelier, and Varro 2.
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OBVIOUSNESS—
TIELEMAN, LETELIER, NATTEL, AND VARRO 2
In rejecting Appellant’s claims 5–9 over Tieleman, Letelier, Nattel,
and Varro 2, the Examiner relied on substantially the same teachings in
Tieleman, Letelier, and Varro 2, discussed above, and cited Nattel as
additional evidence that the claimed process of treating atrial fibrillation
with DEA would have been obvious. See Ans. 10–13.
Appellant’s arguments do not persuade us of error in the Examiner’s
rejection. See Appeal Br. 13. As discussed above, Nattel teaches that DEA
accumulation is important to the therapeutic antiarrhythmic effect of chronic
AMIO treatment, and that DEA can exert a more potent effect than AMIO.
Accordingly, for the reasons discussed above, we find that Nattel bolsters
the suggestion from the collective teachings of Tieleman, Letelier, and
Varro 2 that chronic oral administration of DEA would be a suitable
treatment for atrial fibrillation. For the reasons discussed above, we are also
unpersuaded that the passage on page 207 of Nattel teaches away from
Appellant’s claimed invention.
Accordingly, because Appellant’s arguments do not persuade us of
error in the Examiner’s rejection of claims 5–9 over Tieleman, Letelier,
Nattel, and Varro 2, we affirm that rejection.

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CONCLUSION
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
5–11 103(a) Varro 1, Varro 2,
Tieleman, Letelier
5–11
5–9 103(a) Tieleman, Letelier,
Varro 2
5–9
5–9 103(a) Tieleman, Letelier,
Nattel, Varro 2
5–9
Overall
Outcome
5–11

TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R.
§ 1.136(a)(1)(iv).

AFFIRMED