Ex Parte Aoki et al

Patent Trial and Appeal Board

Aug 23, 2013

11476873 (P.T.A.B. Aug. 23, 2013)

UNITED STATES PATENT AND TRADEMARK OFFICE
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BEFORE THE PATENT TRIAL AND APPEAL BOARD
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Ex parte TARO AOKI and KATSUTOSHI MIYOSAWA
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Appeal 2012-004032
Application 11/476,873
Technology Center 1600
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Before TONI R. SCHEINER, JEFFREY N. FREDMAN, and
ANNETTE R. REIMERS, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving claims to a method
of treatment of diabetes. The Examiner rejected the claims as obvious. We
have jurisdiction under 35 U.S.C. § 6(b). We reverse.

1 Appellants identify the Real Parties in Interest as Kowa Co., Ltd.,
and Nissan Chemical Industries, Ltd. (see App. Br. 1).
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Application 11/476,873

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Statement of the Case
Background
The Specification teaches that “when pitavastatin and enalapril
maleate are used in combination, the effect of improving impaired glucose
tolerance is remarkably enhanced, and the combined use is beneficial for
improving anomalous lipid metabolism and reducing insulin resistance as
well” (Spec. 4).
The Claims
Claims 1, 2, and 9-13 are on appeal2. Independent claim 1 is
representative and reads as follows:
1. A method for treatment of diabetes, comprising
administering an effective amount of pitavastatin
calcium and an effective amount of enalapril maleate to a
subject in need of such treatment.

The issues
A. The Examiner rejected claims 1, 2, and 9 under 35 U.S.C. § 103(a) as
obvious over Takagi,3 Tsuji,4 and Bastin5 (Ans. 5-6).

2 Claim 14 is objected to, and claims 3-8 were cancelled (see App.
Br. 2).
3 Takagi et al., WO 2004/096276 A1, published Nov. 11, 2004. We
reference the machine translation.
4 Tsuji et al., Effect Of Enalapril On Insulin Sensitivity In Patients
With Hypertension And Type 2 Diabetes Mellitus: A Pilot Study
Using The Glucose Clamp Technique, 59 CURRENT THERAPEUTIC
RES. 863-872 (1998).
5 Bastin et al., Salt Selection and Optimisation Procedures for
Pharmaceutical New Chemical Entities, 4 ORGANIC PROCESS RES.
& DEVELOPMENT 427-435 (2000).
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B. The Examiner rejected claims 10-13 under 35 U.S.C. § 103(a) as
obvious over Takagi, Tsuji, Bastin, and Wilkinson6 (Ans. 7-8).
A. 35 U.S.C. § 103(a) over Takagi, Tsuji, and Bastin
The Examiner finds that Takagi “teaches that pitavastatin calcium is
one of the pitavastatin salts that can be used for the treatment of diabetes”
(Ans. 5). The Examiner finds that “Tsujii et. al. teach the treatment of type 2
diabetes mellitus with enalapril” (Ans. 6). The Examiner finds that “Tsujii
does not teach the maleate salt of enalapril. However, Bastin teaches that
making salts of known drugs is routine practice . . . In particular the author
mentions maleate salts” (Ans. 6). The Examiner finds it obvious to
“combine two compositions (pitavastatin calcium and enalapril maleate)
each of which is taught by the prior art to be useful for the same purpose
(treating diabetes and type 2 diabetes in particular), in order to form a third
composition to be used for the very same purpose” (Ans. 6).
The issues with respect to this rejection are:
(i) Does the evidence of record support the Examiner’s conclusion
that Takagi, Tsuji, and Bastin render the claims prima facie 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
1. Takagi teaches “a pharmaceutical composition for the treatment
of diabetes . . . comprising as an active ingredient one or more

6 Wilkinson, G., Pharmacokinetics, in Goodman & Gilman’s The
Pharmacological Basis of Therapeutics 3-29 (2001).
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medicament(s) selected from the group consisting of . . . pitavastatin”
(Takagi ¶ 0009).
2. Takagi teaches that one acceptable salt for pitavastatin is the
calcium salt (see Takagi ¶ 0013).
3. Tsuji teaches that “[i]nsulin sensitivity improved during
enalapril treatment, as evidenced by higher glucose infusion rates during the
hyperglycemic glucose clamp” (Tsuji 871).
4. Bastin teaches that maleate is a common pharmaceutical salt
(see Bastin 428, table 1).
5. Bastin teaches that “[w]here possible, a range of salts should be
prepared for each new substance and their properties compared during a
suitable preformulation program. . . . A well designed salt selection and
optimisation study provides a sound base on which to build a rapid and
economic product development programme” (Bastin, abstract).
6. The Specification teaches that
the dose of each drug component is suitably selected in
consideration of the symptoms. The dose of pitavastatin is
0.1 to 50 mg per day, preferably 1 to 20 mg per day. The
dose of enalapril or a salt thereof is 1 to 50 mg per day,
preferably 2.5 to 20 mg per day. Two components may be
administered once a day or two or more times a day in a
divided manner.

(Spec. 9-10).
7. The Specification teaches that “administration of pitavastatin
and enalapril maleate . . . was found to exhibit a remarkable effect of
improving impaired glucose tolerance, as compared with administration of
another HMG-CoA reductase inhibitor and enalapril maleate” (Spec. 13-14).
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Principles of Law
“In proceedings before the Patent and Trademark Office, the
Examiner bears the burden of establishing a prima facie case of obviousness
based upon the prior art.” In re Fritch, 972 F.2d 1260, 1265 (Fed. Cir. 1992).
“[A]ny need or problem known in the field of endeavor at the time of
invention . . . can provide a reason for combining the elements in the manner
claimed.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 420 (2007).
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
Id. at 416. “[E]vidence rising out of the so-called ‘secondary considerations'
must always when present be considered en route to a determination of
obviousness.” Stratoflex, Inc. v. Aeroquip Corp., 713 F.2d 1530, 1538 (Fed.
Cir. 1983).
Analysis
Prima facie case
Takagi teaches the use of pitavastatin calcium for treatment of
diabetes (FF 1-2) and Tsuji teaches the use of enalapril for treatment of
diabetes (FF 3). Bastin teaches that it is routine to optimize the salts of
pharmaceutical agents and that maleate is a routinely used salt (FF 4-5).
Appellants contend that “the Examiner fails to identify an apparent
reason why a skilled artisan would select pitavastatin calcium from the
various agents in Takagi and then use such selected agent in combination
with enalapril maleate” (App. Br. 5).
We are not persuaded. Both Takagi and Tsuji are directed to
treatment of the same disease (FF 1-3) and Takagi recognizes that “one or
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more medicament(s)” may be used in this treatment (FF 1). The ordinary
practitioner routinely combined diabetes agents for improved or synergistic
effects. See In re Diamond, 360 F.2d 214, 217 (CCPA 1966) (“[I]t is a
standard practice in this art to combine ingredients…. Another advantage of
drug combination is that drugs which produce the same end result may have
entirely different mechanisms of action and in this way combine very
effectively”).
Applying the KSR standard of obviousness to the findings of fact, we
conclude that the person of ordinary creativity would have had a reason to
combine two known drugs for treatment of diabetes, and would also have
had a reason to select known salts of these drugs (FF 1-5).
Unexpected results
Appellants contend that “the improvement in performance of
combined pitavastatin calcium and enalapril maleate in comparison with the
separate performance of the respective agents is significant and better than
would have been expected upon combination of the respective agents” (App.
Br. 6).
The Examiner finds that “Example 1 provides synergistic data for
only one dose: 10 mg/Kg of pitavastatin calcium and 1 mg/Kg of enalapril
maleate. This data is not commensurate in scope with the claims” (Ans. 13).
We find that Appellants have the better position. The Specification
expressly compared the combination of pitavastatin and enalapril maleate
with pravastatin and enalapril maleate and found that the combination was
unexpectedly superior (FF 7). The Specification provides dosing
information regarding this combination which is commensurate with the
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claims (FF 6). In addition, the Aoki Declaration7 teaches that
“administration of pitavastatin and enalapril maleate in combination
provides an unexpected synergistic effect that is not achieved when
pravastatin or simvastatin are administered with enalapril maleate” (Aoki
Dec. 4 ¶ 7).
We are not persuaded by the Examiner’s “commensurate in scope”
argument because the Examiner has provided no reason or evidence to
suggest that different dosing amounts of the same two drugs, optimized to
particular patients, will not also show the same unexpected synergistic
effect. See In re Kao, 639 F.3d 1057, 1068 (Fed. Cir. 2011) (“If an applicant
demonstrates that an embodiment has an unexpected result and provides an
adequate basis to support the conclusion that other embodiments falling
within the claim will behave in the same manner, this will generally
establish that the evidence is commensurate with [the] scope of the
claims.”).
Conclusion of Law
(i) The evidence of record supports the Examiner’s conclusion that
Takagi, Tsuji, and Bastin render the claims prima facie obvious.
(ii) Appellants have presented evidence of secondary considerations,
that when weighed with the evidence of obviousness, is sufficient to support
a conclusion of non-obviousness.
B. 35 U.S.C. § 103(a) over Takagi, Tsuji, Bastin, and Wilkinson
This rejection relies upon the underlying obviousness rejection of
Takagi, Tsuji, and Bastin. Having reversed the rejection of claim 1 over

7 Declaration of Dr. Taro Aoki, filed Jan. 3, 2011.
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Takagi, Tsuji, and Bastin, we necessarily reverse this obviousness rejection,
which does not overcome the unexpected results demonstrated in
Appellants’ Specification (FF 7) and the Aoki Declaration.
SUMMARY
In summary, we reverse the rejection of claims 1, 2, and 9 under 35
U.S.C. § 103(a) as obvious over Takagi, Tsuji, and Bastin.
We reverse the rejection of claims 10-13 under 35 U.S.C. § 103(a) as
obvious over Takagi, Tsuji, Bastin, and Wilkinson.

REVERSED

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