Ex Parte Brunner

Board of Patent Appeals and Interferences

Jan 14, 2010

10911644 (B.P.A.I. Jan. 14, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
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Ex parte HANS R. BRUNNER
__________

Appeal 2009-008383
Application 10/911,644
Technology Center 1600
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Decided: January 14, 2010
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Before TONI R. SCHEINER, DEMETRA J. MILLS, and
LORA M. GREEN, Administrative Patent Judges.

GREEN, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134 from the
Examiner’s final rejection of claims 1-5 and 11. We have jurisdiction under
35 U.S.C. § 6(b).

Appeal 2009-008383
Application 10/911,644

STATEMENT OF THE CASE
Claim 1 is representative of the claims on appeal, and reads as
follows:
1. A pharmaceutical composition in unit dose form, comprising:
(a) a COX-1 inhibitor; and
(b) ifetroban in an amount less than 200 mg;
wherein said COX-1 inhibitor, and said ifetroban are present in a
synergistic unit dosage amount.

The Examiner relies on the following evidence:
Rubin US 5,312,818 May 17, 1994
Tejada US 2003/0050305 A1 Mar. 13, 2003
Klein US 2004/0242597 A1 Dec. 2, 2004

We affirm.

ISSUE
The Examiner concludes that claim 1 is rendered obvious by the
combination of Rubin, Klein, and Tajeda.
Appellant asserts that the Examiner has not established a prima facie
case that the combination of references renders obvious the pharmaceutical
composition of claim 1 “wherein said COX-1 inhibitor, and said ifetroban
are present in a synergistic unit dosage amount.”
Thus, the issue on Appeal is: Has Appellant demonstrated that the
Examiner erred in concluding that the combination of Rubin, Klein, and
Tajeda renders obvious the pharmaceutical composition of claim 1 “wherein
said COX-1 inhibitor, and said ifetroban are present in a synergistic unit
dosage amount?”

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FINDINGS OF FACT
FF1 According to the Specification:
The present invention is based upon the concept that
thromboxane receptor antagonists and COX-1 inhibitors (e.g.,
NSAIDs that act on COX-1) have complementary activities and
may be combined to increase their effectiveness. Thus, the
dosages of these compounds, when administered in
combination, may be decreased below the dosages normally
used in the art and, as a result, the risk of unwanted side effects
can be reduced. For example, lower dosages of COX-1
inhibitors should reduce the gastrointestinal side effects
associated with these drugs.

(Spec. 2.)
FF2 The Specification teaches further:
For the purposes of the present invention these lowered dosages
are referred to as a “synergistic dosage,” “synergistic daily
dosage” and “synergistic unit dosage amount” respectively.
Expressed more precisely, a synergistic dosage of a compound
is a therapeutically effective dosage that is lower than the
minimum effective dose of the same compound (i.e., the lowest
amount that can be given to a patient and still obtain a
beneficial therapeutic effect) when it is the sole active agent
administered.

(Id. at 4.)
FF3 As to dosages, the Specification teaches that “[w]ith respect to
therapeutic agents, it is expected that the skilled practitioner will adjust
dosages on a case by case basis using methods well established in clinical
medicine.” (Id. at 8.)
FF4 The Examiner rejects claims 1-5 and 11 under 35 U.S.C. § 103(a) as
being obvious over the combination of Rubin, Klein, and Tajeda (Ans. 3).
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As Appellant does not argue the claims separately, we focus our analysis on
claim 1, and claims 2-5 and 11 stand or fall with that claim. 37 C.F.R. §
41.37(c)(1)(vii).
FF5 The Examiner relies on Rubin for teaching “a combination comprising
a thromboxan[e] A2 receptor antagonist and an anti-inflammatory agent
used to treat inflammatory conditions such as arthritis, while inhibiting
formation of and/or treating gastrointestinal ulcers.” (Id.)
FF6 The Examiner further finds that Rubin teaches that the thromboxane
A2 receptor antagonist may be ifetroban when certain side groups and bonds
are chosen, and that the anti-inflammatory agent may be indomethacin or
naproxen (id.). Indomethacin and naproxen are COX-1 inhibitors.
FF7 The Examiner also finds that Rubin teaches that the thromboxane A2
receptor antagonist is employed from 0.1 to about 2500 mg and the anti-
inflammatory agent is employed from about 5 to about 1500 mg (id.).
FF8 Rubin teaches:
[A]dverse effects of anti-inflammatory drugs on the
gastrointestinal system seriously limit chronic use thereof. In
accordance with the present invention, it has been found that
thromboxane A2 receptor antagonists inhibit and in some cases,
prevent side effects associated with use of anti-inflammatory
drugs without diminishing the efficacy thereof. Thus,
thromboxane A2 receptor antagonists may be used concurrently
with anti-inflammatory drugs to improve the clinical safety of
such anti-inflammatory drugs.

(Rubin, col. 2, ll. 48-57.)
FF9 The Examiner finds that Rubin does not specifically teach ifetroban or
its amounts (Ans. 4).
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FF10 The Examiner relies on Klein for teaching “the combined
administration of PDE4-inhibitors and NSAIDS for the treatment of
inflammatory diseases or disorders, such as gastric erosions and ulcers.”
(Id.)
FF11 The Examiner finds that Tajeda teaches that thromboxane inhibitors
include ifetroban (id.).
FF12 The Examiner concludes that it would have been obvious to use
ifetroban in the composition of Rubin as the ifetroban is encompassed by the
structure of thromboxane A2 receptor antagonists taught by Rubin (id. at 5).
FF13 As to the limitation “wherein said COX-1 inhibitor, and said ifetroban
are present in a synergistic unit dosage amount,” the Examiner notes that the
ranges of Rubin encompass the range recited in claim 1, and also concludes,
citing In re Boesch, 617 F.2d 272, 276 (CCPA 1980), that it would have
been well within the level of skill of the ordinary artisan to optimize the
amounts of a COX-1 inhibitor and ifetroban in the composition (Ans. 5-6).

PRINCIPLES OF LAW
The question of obviousness is resolved on the basis of underlying
factual determinations including: (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) secondary considerations of
nonobviousness, if any. Graham v. John Deere Co., 383 U.S. 1, 17 (1966).
The Supreme Court has recently emphasized that “the [obviousness]
analysis need not seek out precise teachings directed to the specific subject
matter of the challenged claim, for a court can take account of the inferences
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and creative steps that a person of ordinary skill in the art would employ.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007). Moreover,
When there is a design need or market pressure to solve a
problem and there are a finite number of identified, predictable
solutions, a person of ordinary skill has good reason to pursue
the known options within his or her technical grasp. If this
leads to the anticipated success, it is likely the product not of
innovation but of ordinary skill and common sense.

Id. at 421.
“In cases involving overlapping ranges . . . even a slight overlap in
range establishes a prima facie case of obviousness.” In re Peterson, 315
F.3d 1325, 1329 (Fed. Cir. 2003). In addition, as noted by the Peterson,
“[t]he normal desire of scientists or artisans to improve upon what is already
generally known provides the motivation to determine where in a disclosed
set of percentage ranges is the optimum combination of percentages.” Id. at
1330. “The law is replete with cases in which the difference between the
claimed invention and the prior art is some range or other variable within the
claims.” In re Woodruff, 919 F.2d 1575, 1578 (Fed. Cir. 1990) (citations
omitted). “These cases have consistently held that in such a situation, the
applicant must show that the particular range is critical, generally by
showing that the claimed range achieves unexpected results relative to the
prior art range.” Id.
The burden of demonstrating unexpected results rests on the party
asserting them. In re Klosak, 455 F.2d 1077, 1080 (CCPA 1972).
Moreover, it is well settled that results must be established by factual
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evidence. “Mere argument or conclusory statements in the specification
does not suffice.” In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984).

ANALYSIS
Appellant argues that while the “Rubin reference cites broad ranges of
drug amounts that can be used in compositions . . . . this is not the same as
suggesting that when drugs are combined, they can be used in an amount
lower than their minimum effective dosage (MED) when used alone, i.e., in
a ‘synergistic unit dosage amount.’” (App. Br. 9.) Appellant argues further
that the use of drugs at amounts lower than their MED is not simply
optimization, as “it provides an incentive to use the combination that did not
otherwise exist and in a way that would not normally be expected.” (Id.)
Appellant also argues, citing Richardson Vicks Inc. v. Upjohn Co., 122 F.3d
1476 (Fed. Cir. 1997), that “synergism is not common in drug combinations
and, in fact, has been recognized by the Federal Circuit as an important
factor that must be considered in deciding whether drug combinations are
obvious.” (App. Br. 9.)
Appellant argues further that the claims require that “the COX-1
inhibitor and the ifetroban be present in a synergistic unit dosage amount,”
which, as defined by the Specification, is a therapeutically effective dosage
that is less than the minimum effective dosage when the compound is used
alone (Reply Br. 1-2). Thus, Appellant asserts, that while Rubin teaches
synergistic amounts of drugs, “it says nothing at all with respect to synergy
as this term is defined in the application.” (Id. at 2.) Moreover, Appellant
asserts, if one were optimizing amounts based on based on Rubin, they
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would be optimizing “the ability of one drug to reduce a side effect of
another, not with any therapeutic effect that the drugs have alone.” (Id.)
Appellant’s arguments have been carefully considered, but are not
convincing. Rubin teaches compositions that encompass the amounts
required by the claimed composition. Thus, in the absence of unexpected
results, the claimed composition is prima facie obvious over the composition
taught by the combination of references as set forth by the Examiner.
As to Appellant’s argument that the combination does not teach
“wherein said COX-1 inhibitor, and said ifetroban are present in a
synergistic unit dosage amount” as defined by the Specification, we agree
with the Examiner that it would have been obvious to optimize the amounts
of each of the components of the composition to obtain the optimal
therapeutic result. The Specification supports that such optimization is
routine by teaching that “[w]ith respect to therapeutic agents, it is expected
that the skilled practitioner will adjust dosages on a case by case basis using
methods well established in clinical medicine.” (FF3.) In addition, while
Appellant asserts that if one were optimizing amounts based on the teachings
of Rubin, one would optimize the ability of one drug to reduce a side effect
of another, and not with therapeutic effect that the drugs have alone, the
Specification also teaches that one of the goals of the instant composition is
to decrease dosages below those normally used in the art, thus reducing the
risk of unwanted side effects, such as the gastrointestinal side effects
associated with COX-1 inhibitors. (FF1.)
Moreover, in Richardson Vicks, the Federal Circuit found that
Examiner had placed “singular reliance on the evidence of synergy to allow
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the claims.” 122 F.3d at 1482. The Examiner found, in allowing the patent
at issue, that the evidence of synergy was unexpected, and thus was
sufficient to rebut the prima facie case of obviousness. Id. Appellant
therefore appears to be arguing, based on their reliance on that case, that the
claimed composition exhibits unexpected results. Appellant has not
presented, however, any evidence of unexpected results, and mere argument
that the claimed composition exhibits “synergy” and thus “unexpected
results” is not sufficient to rebut the prima facie case.

CONCLUSION(S) OF LAW
We conclude that Appellant has not demonstrated that the Examiner
erred in concluding that the combination of Rubin, Klein, and Tajeda renders
obvious the pharmaceutical composition of claim 1 “wherein said COX-1
inhibitor, and said ifetroban are present in a synergistic unit dosage amount.”
We thus affirm the rejection of claim 1 under 35 U.S.C. § 103(a) as
being obvious over the combination of Rubin, Klein, and Tajeda. As claims
2-5 and 11 stand or fall with claim 1, we affirm the rejection as to those
claims as well.

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)(1)(iv)(2006).

AFFIRMED
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LAW OFFICE OF MICHAEL A. SANZO, LLC
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