Ex Parte Thuillez et al

Patent Trial and Appeal Board

Sep 22, 2016

13134667 (P.T.A.B. Sep. 22, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
13/134,667 06/14/2011
25666 7590 09/22/2016
THE FIRM OF HUESCHEN AND SAGE
SEVENTH FLOOR, KALAMAZOO BUILDING
107 WEST MICHIGAN A VENUE
KALAMAZOO, MI 49007
Christian Thuillez
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
SERVIER 584 US 5416
EXAMINER
SHEN, WU CHENG WINSTON
ART UNIT PAPER NUMBER
1628
MAILDATE DELIVERY MODE
09/22/2016 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte CHRISTIAN THUILLEZ, PAULUS MULDER,
JEAN-PAUL VILAINE, MARIE DOMINIQUE FRATACCI,
GUY LEREBOURS-PIGEONNIERE, LUC FELDMANN,
and JEROME ROUSSEL
Appeal2014-007336
Application 13/134,667
Technology Center 1600
Before JEFFREY N. FREDMAN, TA WEN CHANG, and
RYAN H. FLAX, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1 under 35 U.S.C. § 134 involving claims to a method
of treating heart failure. The Examiner rejected the claims as obvious. We
have jurisdiction under 35 U.S.C. § 6(b). We affirm.
Statement of the Case
Background
"The present invention relates to the use of the association of a
selective and specific sinus node Ir current inhibitor and an agent that
1 Appellants identify the Real Party in Interest as LES LABORATOIRES
SERVIER (see App. Br. 3).
Appeal2014-007336
Application 13/134,667
inhibits angiotensin-converting enzyme (ACE inhibitor) in obtaining
medicaments intended for the treatment of heart failure" (Spec. 1: 1-3).
The Claims
Claims 1, 2, 4, 5, 7-9, 11, 12, and 14--16 are on appeal. As
Appellants do not argue the claims separately, we focus our analysis on
claim 1, and claims 2, 4, 5, 7-9, 11, 12, and 14--16 stand or fall with that
claim. Independent claim 1 is representative and reads as follows:
1. A method of treating heart failure in a subject in need
thereof, comprising administration of an effective amount of a
composition comprising a combination of a selective and
specific sinus node Ir current inhibitor selected from ivabradine,
its addition salts with a pharmaceutically acceptable acid,
hydrates and crystalline forms thereof, andN-{[(7S)-3,4-
dimethoxybicyclo[ 4.2.0]octa-1,3,5-trien-7-yl]methyl }-3-(7 ,8-
dimethoxy-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl)-N-
methyl-3-oxo-1-propanamine, its addition salts with a
pharmaceutically acceptable acid, hydrates and crystalline
forms thereof and an agent that inhibits angiotensin=converting
enzyme selected from perindopril, its addition salts with a
pharmaceutically acceptable base, hydrates and crystalline
forms thereof, wherein the composition optionally comprises
one or more pharmaceutically acceptable excipients.
The Issue
The Examiner rejected claims 1, 2, 4, 5, 7-9, 11, 12, and 14--16 under
35 U.S.C. § 103(a) as obvious over Brugts,2 Peglion,3 Reil,4 and Horvath5
(Final Act. 2--4).
2 Brugts et al., Angiotensin-converting enzyme inhibition by
perindopril in the treatment of cardiovascular disease, 7 EXPERT REV.
CARDIOVASC. THERAPY 345-360 (2009) ("Brugts").
3 Peglion et al., US 2009/0069296 Al, published Mar. 12, 2009 ("Peglion").
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Application 13/134,667
The Examiner finds that Brugts teaches "perindopril is a known ACE
inhibitor ... and is useful to treat diastolic heart failure"; Reil teaches
"ivabradine inhibits Ir channels and reduces heart rate"; Horvath teaches
"ivabradine and its salts are effective to treat heart failure"; and Peglion
teaches N-{[(7 S)-3,4-dimethoxybicyclo[ 4.2.0]octa-1,3,5-trien-7-yl]methyl}-
3-(7 ,8-dimethoxy-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl)-N-methyl-3-
oxo-1-propanamine compounds "are useful for treating heart failure,
including that of diastolic origin" (Final Act. 3).
The Examiner acknowledges that the prior art does not "disclose
combining perindopril with the claimed sinus node Ir current inhibitor" but
finds it obvious "to administer the combination to treat heart failure with
preserved systolic function" (Final Act. 3--4 ).
The issues with respect to this rejection are:
(i) Does the evidence support the Examiner's conclusion that
Brugts, Peglion, Reil, and Horvath render claim 1 obvious?
(ii) If so, have Appellants presented evidence of secondary
considerations, that when weighed with the evidence of obviousness, is
sufficient to support a conclusion of non-obviousness?
Findings of Fact
Prima F acie Case
4 Reil et al., Heart Rate Reduction by 1.rChannel Inhibition and its Potential
Role in Heart Failure with Reduced and Preserved Ejection Fraction, 19
TRENDS CARDIOVASC. MED. 152-157 (2009) ("Reil").
5 Horvath et al., US 2007/0082885 Al, published Apr. 12, 2007 ("Horvath").
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1. Brugts teaches: "Perindopril is one of the ACE inhibitors that
has been extensively studied in randomized clinical trials within various
patient populations. The clinical efficacy has been demonstrated in patients
with ... stable coronary artery disease (CAD) and heart failure. Perindopril
has a positive safety and tolerability profile." (Brugts, Abstract).
2. Brugts teaches that in cerebrovascular disease "the combination
of the two drugs, perindopril and indapamide, was associated with the
beneficial effects, as single therapy was not associated with significant
treatment benefits" (Brugts 352, col. 1 ).
3. Peglion teaches synthesis of N-{[(7 S)-3,4-
dimethoxybicyclo[ 4.2.0]octa-1,3,5-trien-7-yl]methyl }-3-(7 ,8-dimethoxy-
1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl)-N-methyl-3-oxo-1-propanamine
in example 3a (Peglion i-fi-f 192-196).
4. Peglion teaches "compounds [that] may especially improve the
treatment and long-term prognosis of ischaemic cardiopathies in their
various clinical manifestations: ... heart failure whether systolic or diastolic
and whether in the chronic or acute forms thereof' (Peglion i169).
5. Reil teaches "[a]mong these newly identified HR-lowering
drugs, only ivabradine has now become approved for clinical use. Ir-channel
inhibition mainly reduces HR, thereby improving myocardial oxygen
supply, energy balance, and cardiac function" (Reil, Abstract).
6. Reil teaches "HR reduction by Ir-channel inhibition would fit
the therapeutic concept of improving impaired L V diastolic filling as well as
decreasing inappropriate high Ea" (Reil 155, col. 3).
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Application 13/134,667
7. Horvath teaches: "Ivabradine, and addition salts thereof with a
pharmaceutically acceptable acid, and more especially its hydrochloride,
have very valuable pharmacological and therapeutic properties, especially
bradycardic properties, making those compounds useful in the treatment or
prevention of ... heart failure" (Horvath i-f 2).
Secondary Considerations
8. The Specification teaches, "[h ]eart failure was induced in rats
by ligature of the left coronary artery . . . The animals recuperate for 7 days
and then, for 12 weeks, they are given either 3 mg/kg of compound A, or 0.4
mg/kg of perindopril, or perindopril and compound A concomitantly" (Spec.
7, 11. 12-16).
9. Table 3 of the Specification is reproduced below:
Table 3
Control
L VESP (mm Hg) 140
dP/dt...~x ( 1 o·jmm Hg/s) 992
LVESPVR (mm Hg/RVU) 26.4
LVE.DP {mm Hg) 1.86
dP/dtrn;11 (-10
3mm Hg!s) 10.24
tau {ms) 3.54
LVEOPVR (mm Hg/RYU} 0.84
HF
{untreated)
120
6.89~
11 1 ~
HF +A
i18
6.78
5.87
HF+ HF+ A+
perindopril perindopril
99 105
5.97 7.69 ___ ,,,,,,,,,,,,,,,,,,,,,,,,,,.
16.4;
5.11 6.19
-------------------------------------
8.37t
• p<0.05 vs comrol; r p<0.05 vs HF; t p<0.05 vs HF ;-A ~~-;r~·s HF+perindopril
Table 3 shows:
It is found that treatment of the animals which have heart
failure, whether with perindopril on its own or with compound
A on its own, improves systolic function, which can be seen
from the LVESPVR, the only load-independent parameter. The
end diastolic pressure and relaxation time are clearly improved
by perindopril on its own or by compound A on its own, and a
tendency to a further reduction in those two parameters is noted
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when the two substances are administered together. The
compliance of the left ventricle (measured by L VEDPVR), the
only load-independent parameter, is very clearly improved by
perindopril and by compound A. Surprisingly, this effect is
significantly increased when the animals are given the two
treatments concomitantly.
(Spec. 9: 1-9).
10. The Specification does not provide the dosage information for
either perindopril or ivabradine used for treatment of heart failure in tables
4a and 4b (see Spec. 9-10).
11. Tables 4a and 4b of the Specification are reproduced below:
Table 4a
Hf HF+-
_________ C_o_. n_tr_o_l _ _.(.__u_nt_rn_a_te_-d~}-P~,~indoprll
LVESP {mm Hg) 163 134• 1021· --............................................................................... ____ .__...... ............................ ..
dPldtm.~ ( 1 O~mm Hg/s) 6.08t
HF+
ivabradine +
perindopril
1oot
6.101
........................... ,,,,,,,, _____ _
LVESPVR (mm HglRVU) 20.2 6.6~ 14.51 12.6tt
LVEDP (mm Hg) 3 . .29 13.93~
i0.63 5.54~ 4.99 4.97
""""··········································"""'""""·······--··································""'""""""""""' _______ _
tau (ms} 3 .. 21 14.29* s.s2t
lVEDPVR (mm Hg/RVU) 0.79 4.06*
Table4b
HF HF+-
Control (untreated) in~~~~-!!:'.~ ...
LVESPVR (mm Hg/RVU} 35,53 9,66"' 20.63*t
LVEDPVR {mm Mg/RYU} 0.85 5.33"' u~rt
[T]reatment with perindopril on its own or in association with
ivabradine improves the systolic function (Table 4a and Figure 4a).
With respect to the diastolic dysfunction, treatment with perindopril
and ivabradine is clearly more effective than perindopril on its own
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(the effect of ivabradine on its own is comparable to that of
perindopril on its own, cf. Table 4b and Figure 4b ).
(Spec. 9: 19-23).
12. Roussel Deel. 16 states:
These experiments [in Figures 3 and 4 of the Specification]
show that the association of ivabradine and perindopril or
compound A and perindopril makes possible an improvement
in diastolic fonction which is greater than that obtained with
one of those two treatments used on its own (synergistic effect),
this improvement allowing a return to normal diastolic function.
This effect was not predictable.
(Roussel Deel. I 2).
13. Chou7 teaches: "The P value? A combined effect greater than
each drug alone does not necessarily indicate synergism. Sometimes this can
be a result of additive effect or even a slight antagonism" (Chou 441, col. 1 ).
14. Chou teaches that the "additive effect of two drugs is not the
simple 'arithmetic sum' of effects of two drugs. If (D)1 and (D)2 inhibits
30% and 10%, respectively, the additive effect is not 70%, because if they
inhibit 60% and 70%, respectively, the additive effect cannot be 130%!"
(Chou 441, col. 1 ).
15. Chou teaches "[fJor any determination of synergy, we need to
know both the potency and the shape of the dose-effect curve of each drug"
(Chou 444, col. 1 ).
6 Declaration of Dr. Jerome Roussel, dated Mar. 13, 2013 ("Roussel Deel.
I").
7 Chou, T., Drug Combination Studies and Their Synergy Quantification -
Using the Chou-Talalay Method, 70 CANCER RES. 440-446 (2010)
("Chou").
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Application 13/134,667
16. Berenbaum8 teaches:
Suppose that two drugs, A and B, each suppress a response by
10% when given at a dosage of 1 mg/kg but that, when both are
given together at this dose, the suppression is not 20 but 90%.
One might conclude that this is a case of marked synergy but,
as the dose-effect curves of these drugs show ... a 2 mg dose
of either drug alone also produces a 90% suppression. As 2 mg
of the combination produces exactly the same effect as 2 mg of
either drug by itself, the drugs are clearly not more effective
when used in combination than when used singly.
(Berenbaum 2).
17. Berenbaum teaches:
[An approach assuming that the effect of a combination to be
the sum of effects of its constituents] would be correct only if
the effects of drugs were simply proportional to dose, when the
effect of a dose of one drug would be the sum of the effects of
its constituent quanta. If two or more such drugs given together
did not interact pharmacologically, the effect of the
combination should similarly be the sum of effects of its
constituent quanta. However, because of the nature of drug-
receptor interactions, dose-effect curves for biologically active
agents are rarely if ever linear.
(Berenbaum 2).
18. Roussel Dec. II9 states
we are of the opinion that Chou's article is not sufficient to
reject the synergy we claim for our drug combination. In our
model of diastolic dysfunction, permanent coronary ligature
induces a transmural infarct representing 40 % of the left
ventricle. This necrotic part of the ventricle cannot be salvaged
8 Berenbaum, M., Synergy, additivism and antagonism in
immunosuppression, 28 CLIN. EXP. IMMUNOL. 1-18 (1977) ("Berenbaum").
9 Declaration of Dr. Jerome Roussel, dated Oct. 7, 2013 ("Roussel Deel. II").
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by any treatment to date. This cardiomyocytes major loss is
responsible for the serious impairment of cardiac function. Any
treatment given after infarct scar formation (7 days) can only
improve the functioning of the remaining 60% of the
ventricular wall. Perindopril and If inhibitors are separately
efficient in improving diastolic function, as exhibited by
LVEDPVR reduction, and reach similar maximal effects. As
expected considering the large myocardial injury, a diastolic
dysfunction still remains. Perindopril and Ir inhibitors
administered in combination exert a further reduction of this
parameter, which was not expected; neither was expected that
they jointly reduce LVEDPVR to the level of healthy animals.
(Roussel Dec. II).
Principles of Law
"The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results."
KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).
"[E]vidence rising out of the so=called 'secondary considerations'
must always when present be considered en route to a determination of
obviousness." Stratojlex, Inc. v. Aeroquip Corp., 713 F.2d 1530, 1538 (Fed.
Cir. 1983).
Analysis
We adopt the Examiner's findings regarding the scope and content of
the prior art (Final Act. 2--4; FF 1-18) and agree that the claimed method
would have been obvious over the teachings of Brugts, Peglion, Reil, and
Horvath.
Prima F acie Obviousness
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The Examiner has established a prima facie case that combining
perindopril (FF 1-2) with either N-{[(7 S)-3,4-dimethoxybicyclo[ 4.2.0]octa-
1,3,5-trien-7-yl]methyl }-3-(7 ,8-dimethoxy-1,2,4,5-tetrahydro-3H-3-
benzazepin-3-yl)-N-methyl-3-oxo-1-propanamine (FF 3--4) and ivabradine
(FF 5-7) for treatment of heart failure would have been obvious because
each compound is known as useful in treating heart failure or improving
cardiac function (FF 1, FF 4---6), combination therapies were known (FF 2)
and would have been combined in order "to administer the combination to
treat heart failure with preserved systolic function" (Final Act. 3--4). See In
re Kerkhoven, 626 F.2d 846, 850 (CCPA 1980).
Unexpected Results
Appellants contend that "the instant specification discloses data
demonstrating the superior and unexpected effects associated with the
combinations recited in the instant claims" (App. Br. 7). Appellants contend
that the "pharmacological data disclosed at pages 7-10 of the instant
specification demonstrate that combinations comprising perindopril ...
exhibit significantly improved effects for the treatment of heart failure with
preserved systolic function compared to monotherapy with perindopril and
either of the sinus node Ir current inhibitors" (id.).
Appellants further contend that the Roussel Deel. I
provides a detailed analysis of the disclosed heart failure animal
model data in view of the etiology of the disease, explaining
that, in contrast to monotherapy, treatment with combinations
comprising perindopril and ivabradine or perindopril and N-
{[(7 S)-3,4-dimethoxybicyclo[ 4.2.0]octa-1,3,5-trien-7-
yl]methyl }-3-(7 ,8-dimethoxy-1,2,4,5-tetrahydro-3H-3-
benzazepin-3-yl)-N-methyl-3-oxo-1-propanamine results in
improvements in diastolic function which allows for a return to
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normal diastolic function. ROUSSEL Declaration 1 further
explains that such results were not predictable.
(App. Br. 7). Appellants further contend that Roussel Deel. II "further
explains the data/results disclosed in the specification" teaching that "when
perindopril and the Ir inhibitors are administered in combination, L VEDPVR
(i.e., left ventricle compliance) is returned to the level of healthy animals,
which result would not have been expected by one skilled in the art" (Reply
Br. 3--4).
The Examiner responds that the "only instance in which the
combination of compound A and perindopril is statistically superior to
either drug individually is with the left ventricular end diastolic pressure
volume relation, or L VEDPVR" (Ans. 5). The Examiner "notes that the
term 'synergy' was never mentioned in the specification as filed. It was first
mentioned in Appellants' reply (filed on 03/29/2013)" (Ans. 6).
The Examiner finds that "Appellants have not provided anything other
than argument and conclusory statements when asserting unexpectedly
superior properties as synergy" (Ans. 7). The Examiner finds that "the
disclosures of Chou and Berenbaum [] provide adequate evidence to
contradict Appellants' assertion of synergy" (id.).
We find that, on the evidence of record, the Examiner has the better
position. Appellants' asserted evidence of synergy, and consequent
unexpected result, is based on tables 3, 4a, and 4b of the Specification (FF 9
and 11 ). The data in table 3 was generated by administering a single dosage
of "either 3 mg/kg of compound A, or 0.4 mg/kg of perindopril, or
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perindopril and compound A concomitantly" (FF 8), while tables 4a and 4b
lack any dosage information (FF 10).
Synergism has been defined as "the combined action of two or more
agents ... that is greater than the sum of the action of one of the agents
alone." In re Kollman, 595 F.2d 48, 52 (CCPA 1979). Chou and Berenbaum
clarify that synergism is not, however, any improvement that results from
combining two agents, particularly when the data is based on a single dose
of each agent, but rather requires dose response curve evidence (FF 13-1 7).
Applying Berenbaum's explanation of synergy (FF 16) to the
experimental results displayed in Table 3 of the Specification (FF 8-9),
Table 3 demonstrates that a single dose of compound A, here 3 mg/kg,
results in an L VEDPVR value of 2. 70, while a single dose of perindopril,
here 0.4 mg/kg, results in an L VEDPVR value of 2.36. Table 3 shows that
the combination of 3 mg/kg compound A and 0.4 mg/kg perindopril results
in a L VEDPVR value of 1.37.
However, as Berenbaum points out, without dose response curves for
each drug separately, the data does not necessarily demonstrate synergy (FF
16), because it may be that doubling the dose of either compound A alone to
6 mg/kg or of perindopril alone to 0.8 mg/kg would yield the same reduction
of the LVEDPVR value to approximately 1.37 shown in Table 3 (which
would predict the experimental results). Berenbaum notes that "dose-effect
curves for biologically active agents are rarely if ever linear" (FF 17).
Without such data, we cannot determine on the evidence of record whether
the Appellants' described results were expected or unexpected.
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Therefore, Appellants' data in Tables 3, 4a, and 4b that provide test
data for a single dose (undisclosed doses in Tables 4a and 4b) of each drug
does not demonstrate synergy, but rather simply demonstrates that providing
more active ingredient yields more effect. That is the expected result when
administering active agents, that higher doses yield greater effects. See
Galderma Laboratories, L.P. v. Tolmar, Inc., 737 F.3d 731, 738 (Fed. Cir.
2013) ("[I]ncreasing the dose ... would result in a concomitant increase in
side effects.")
In order to demonstrate synergy, Appellants would need to present
data demonstrating that doubling the dose of either compound A or
perindopril does not result in an LVEDPVR value approximately or better
than the 1.37 shown in Table 3, and that only the combination of a dose of
both of these agents is capable of obtaining the result. This is the express
teaching on synergy found in Berenbaum and supported by Chou (FF 13-
17).
We recognize, but find unpersuasive, Appellants' argument that "the
disclosure in the Chou reference that a combined effect greater than each
drug alone does not necessarily indicate synergism, does not negate the fact
that the data disclosed in the instant specification demonstrate the superior
and unexpected effects associated with the combinations recited" (App. Br.
8).
In fact, the disclosure in Chou does precisely that. As Chou explains,
simple addition (or subtraction) cannot be used to determine synergy
because a hypothetical analysis of two drugs, one with 60% inhibition and
the other with 70% inhibition, when added would yield the impossible result
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of 130% inhibition (FF 14). Chou teaches that "[f]or any determination of
synergy, we need to know both the potency and the shape of the dose-effect
curve of each drug" (FF 15). Appellants' data in the Specification provides
neither the potency nor the shape of the dose-effect curve (FF 9, 11). As
already noted, there is not even data demonstrating that the effect isn't based
solely on increased drug dosage, rather than synergy (see FF 16).
We recognize, but find unpersuasive, Appellants' argument that:
the Berenbaum reference (from 1977) relates to analyzing
synergy in the field of immunology/immunosuppression.
Appellant submits that one skilled in the art would not look to a
reference relating to immunosuppressive agents, which dates
back to 1977, to determine whether or not the results disclosed
in the instant specification, relating to the effects of the
combinations recited in the instant claims in the treatment of
heart failure, are unexpected.
(App. Br. 11 ).
The age of the Berenbaum reference is irrelevant, but Berenbaum' s
teaching regarding the general analysis of whether drugs are synergistic or
not is highly relevant (FF 16-17). Berenbaum provides persuasive
reasoning explaining why single values of drug dosing provide insufficient
information to determine whether the combination of two drugs
demonstrates synergy (FF 16-17). Berenbaum's analysis is reasonably
applicable to any drug that has non-linear dose effects, and Appellants
provide no evidence as to the dose-response curves for either compound A,
perindopril, or ivabradine.
We recognize, but find unpersuasive, Appellants' argument "in
ROUSSEL Declaration 2 that the definition/scientific view on synergy
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disclosed in Chou is not sufficient to rebut the synergy associated with the
combinations recited in the instant claims" (Reply Br. 4).
We have considered the Roussel Declarations, both of which state that
the claimed drug combinations result in synergistic effects (FF 12, 18), and
in particular, the statements in the Roussel Deel. II that "we are of the
opinion that Chou's article is not sufficient to reject the synergy we claim for
our drug combination" because "Perindopril and Ir inhibitors administered in
combination exert a further reduction of [LVEDPVR], which was not
expected" (FF 18).
However, neither Roussel Declaration sufficiently addresses the
specific issues regarding synergism raised by Chou and Berenbaum, who
both explain that the comparison of single data points as in the instant data is
insufficient to demonstrate synergism and that comparison of dose-response
curves are necessary (FF 13-17). Indeed, the Roussel Declarations and
evidence in the Specification do not address the concern clearly explicated
by Berenbaum that simply doubling the dosage of a single drug may yield
the same degree of improvement as administering single dosages of two
different drugs (FF 16). Without such evidence showing the effect of
doubling the dosage of perindopril or one of the If inhibitors, there is no
reason to believe that the improved LVEDPVR values are the result of
anything other than administration of more drug, rather than synergism
between drugs.
Neither Roussel Declaration provides any evidence or reasoning to
explain why the views of Chou and Berenbaum, based on detailed reasoning
and evidence (FF 13-17), were wrong. Instead, the Roussel Deel. I simply
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states that the result is synergistic (FF 12) and the Roussel Deel. II simply
states that Chou's views are controversial and insufficient to "reject the
synergy" (FF 18). However, Roussel Deel. II provides no evidence that
methods by other authors would demonstrate the results in Tables 3, 4a, and
4b are synergistic, nor does Roussel Deel. II provide any reasoning directly
rebutting either Chou or Berenbaum. Therefore, as we balance the relatively
conclusory statements in the two Roussel Declarations with the detailed
analyses provided in the Chou and Berenbaum references, we find that "each
of these affidavits fails in its purpose because each merely contains
unsupported conclusory statements" In re Wright, 999 F.2d 1557, 1563
(Fed. Cir. 1993) that are insufficient to outweigh the more detailed analysis
and reasoning found in Chou and Berenbaum (FF 13-17).
As a final point, the synergism evidence is drawn to the administration
of specific amounts of drug in a specific animal model, and is not
commensurate in scope with the breadth of claim 1 that is open to treatment
using a variety of drug amounts in a variety of subjects. See In re Harris,
409 F.3d 1339, 1344 (Fed. Cir. 2005) (Unexpected results must be
"commensurate in scope with the degree of protection sought by the claimed
subject matter.").
Conclusion of Law
(i) The evidence support the Examiner's conclusion that Brugts,
Peglion, Reil, and Horvath render claim 1 obvious.
(ii) Appellants have not presented evidence of secondary
considerations, that when weighed with the evidence of obviousness, is
sufficient to support a conclusion of non-obviousness.
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SUMMARY
In summary, we affirm the rejection of claim 1 under 35 U.S.C.
§ 103(a) as obvious over Brugts, Peglion, Reil, and Horvath. Claims 2, 4, 5,
7-9, 11, 12, and 14--16 fall with claim 1.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).
AFFIRMED
17