Ex Parte Ohyama et al

Board of Patent Appeals and Interferences

Aug 17, 2007

10111422 (B.P.A.I. Aug. 17, 2007)

The opinion in support of the decision being entered today
is not binding precedent of the Board.

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________

Ex parte TOSHINORI OHYAMA, MASAHIKO OHISHI,
and YASUHIRO YAMAMOTO
____________

Appeal 2007-2396
Application 10/111,422
Technology Center 1600
____________

Decided: August 17, 2007
____________

Before DEMETRA J. MILLS, LORA M. GREEN, and RICHARD M.
LEBOVITZ, 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 1-4, 6, and 9-13. We have jurisdiction
under 35 U.S.C. § 6(b). Claim 1 is representative of the claims on appeal,
and reads as follows:
Appeal 2007-2396
Application 10/111,422

1. An oral solid pharmaceutical in tablet form comprising 0.025 to 2 mg
of 4-(2-methyl- 1-imidazoly1)-2,2-diphenylbutylamide as an active
ingredient, excipient, binder, lubricant and coating agent, which is obtained
by spraying a solution of the active ingredient and the binder on the
excipient, granulating and then drying the resultant mixture, pressing the
granulated and dried mixture to give a plane tablet in the presence of the
lubricant, and then coating the plane tablet with the coating agent to give a
coated tablet, wherein the coating agent comprises titanium dioxide and
ferric oxide in an mg-equivalent ratio of between 43:7 and 52:8.

The Examiner relies upon the following references:
Miyachi US 5,932,607 Aug. 3, 1999
Parikh US 5,948,437 Sep. 7, 1999
Fukuta EP 0 901 787 Mar. 17, 1999
We reverse.
BACKGROUND
The present invention relates to an oral solid pharmaceutical with a
small amount of powder of 4-(2-methyl-1-imidazoly1)-2,2-
diphenylbutylamide (KRP-197), which has anticholinergic activity on the
bladder and may also be used as a therapeutic drug for pollakiuria and
urinary incontinence (Specification 1).
According to the Specification
KRP-197 is a novel derivative having selective
anticholinergic activity . . . and is promising as a therapeutic
drug for pollakiuria and urinary incontinence . . . . No oral
solid pharmaceutical that is uniform in the content of a small
amount of active ingredient, excellent in the stability and
capable of taking quantitatively on clinical application of KRP-
197 has been known.
The subject of the invention is to provide an oral solid
pharmaceutical that is uniform in the content of active
ingredient contained in a small amount and capable of taking
quantitatively. Additionally, since KRP-197 becomes unstable
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to light under the influence of additives, the subject is to
provide an oral solid pharmaceutical with excellent stability to
light.

(Id.)
According to the method of the invention,
by formulating a small amount of powder of KRP-197 with
drug-making carriers and making into [a] tablet, a
pharmaceutical easy to take quantitatively can be provided.
Moreover, by using polyvinyl pyrrolidone as a binder and
further by coating with a coating solution containing titanium
dioxide and ferric oxide, a pharmaceutical with uniform content
and good light stability can be provided.

(Id. at 2.)
DISCUSSION
Claims 1-4, 6, and 9-13 stand rejected under 35 U.S.C. § 112, first
paragraph, as failing to comply with the written description requirement, i.e.,
for containing new matter.
The Examiner asserts that the language “the coating agent comprises
titanium dioxide and ferric oxide in an mg-equivalent ratio of between 43:7
and 52:8” added by amendment is new matter (Answer 3). Specifically, the
Examiner argues that “[a]lthough the [E]xaminer notes that [A]pplicant has
support for the specific values of 43:7 and 52:8 respectively, [A]pplicant
does not have support for values in between since the [S]pecification does
not disclose a general range.” (Id.)
The disclosure as originally filed need not provide “in haec verba
support for the claimed subject matter at issue,” rather, the disclosure should
convey to one skilled in the art that the inventor had possession of the
invention at the time of filing. Purdue Pharma L.P. v. Faulding
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Pharmaceutical Co., 230 F.3d 1320, 1323, 56 USPQ2d 1481, 1483 (Fed.
Cir. 2000) (citations omitted).
As noted by Appellants, “it . . . is incongruous to find that Applicants
were in possession of a titanium dioxide to ferric oxide ratio of
approximately 6 1/7:1 and a corresponding ratio of 6 ½:1, but were not in
possession of an intermediate ratio therebetween.” (Reply Brief 2.) We
agree, and the rejection is reversed.
Claims 1-4, 6, and 9-13 stand rejected under 35 U.S.C. § 103(a) as
being obvious over the combination of Miyachi and Fukuta.
Miyachi is cited for disclosing the instant imadazole derivative and
pharmaceutical compositions containing the derivative (Answer 3). Miyachi
is also cited for teaching that the imadazole derivative may be mixed with
inert carriers in the formulation of the pharmaceutical compositions, and that
the compositions may be formulated into tablets, capsules, granules, and
powders for oral administration (id.). Miyachi teaches further that the
compounds taught by the patent, such as the instant imadazole derivative,
show an inhibitory effect at a dose of 0.03 mg/kg for bladder contractions
and 0.06 mg/kg for diarrhea (id.). The Examiner acknowledges that
“Miyachi does not specify the excipients or a coating formulation.” (Id.).
Fukuta is cited for teaching a stabilized pharmaceutical composition
that is coated with a composition that comprises inorganic oxides, wherein
the coating protects the composition from light and heat, further providing
storage stability (id.). Fukuta is also cited for its teaching of conventional
excipients, binders, lubricants, and disintegrators (id. at 3-4). The Examiner
specifically points to Table 2 of Fukuta which teaches a coating composition
comprising 0.04 mg of titanium dioxide and 0.008 mg of ferric oxide.
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The Examiner concludes:
It would have been obvious to one of ordinary skill in the
art at the time the invention was made to combine the teachings
of Miyachi and Fukuta [ ] instant coating formulation and
utilize the instant excipients. One would have been motivated
to do so since Fukuta teaches the . . . coating formulation
comprising oxide of inorganic compounds provides storage
stability to a pharmaceutical composition. Thus, it is
considered prima facie obvious to utilize the instantly claimed
coating composition to provide for a storage stable composition
that is protected from light and heat.

(Id. at 4.)
As to the ratio of titanium dioxide to ferric oxide, the Examiner
asserts:
With regard to the instantly claimed ratio, the
manipulation of the concentration of titanium dioxide to ferric
oxide is obvious to one of ordinary skill in the art. One would
have been motivated manipulate the concentration during
routine experimentation and the optimization process. It should
be noted that generally difference in concentrations do not
support the patentability of subject matter encompassed by the
prior art unless there is evidence indicating such as
concentration is critical. See In re Aller, 220 F.2d 454, 456,
105 USPQ 233, 235 (CCPA 1955).

(Id.)
“In rejecting claims under 35 U.S.C. § 103, the examiner bears the
initial burden of presenting a prima facie case of obviousness. Only if that
burden is met, does the burden of coming forward with evidence or
argument shift to the applicant.” In re Rijckaert, 9 F.3d 1531, 1532,
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28 USPQ2d 1955, 1956 (Fed. Cir. 1993) (citations omitted). In order to
determine whether a prima facie case of obviousness has been established,
we considered the factors set forth in Graham v. John Deere Co., 383 U.S.
1, 17 (1996); (1) the scope and content of the prior art; (2) the differences
between the prior art and the claims at issue; (3) the level of ordinary skill in
the relevant art; and (4) objective evidence of nonobviousness, if present.
Appellants argue that Fukuta “evidences no disclosure or suggestion
of any benefit from using a combination of titanium oxide and ferric oxide.
While the Examiner points to Table 2 therein, which exemplifies a tablet
containing both titanium oxide and ferric oxide, the ratio of titanium oxide to
ferric oxide is 0.4:0.008, or 50:1, which is substantially greater than the
upper limit of the presently-recited ratio range.” (Br.1 7.) We agree, and the
rejection is reversed.
The Examiner argues cites In re Aller, 220 F.2d 454, 456, 105 USPQ
233, 235 (CCPA 1955) in the rejection to support the assertion that
“generally difference[s] in concentrations do not support the patentability of
subject matter encompassed by the prior art unless there is evidence
indicating such as concentration is critical.” (Answer 4.) The Examiner
asserts further that “Fukuta teaches a coating composition comprising 20g of
titanium dioxide and 0.4g ferric oxide in example 1 and 2 and a ratio of
titanium dioxide to ferric oxide of 0.4mg:0.008mg. Thus, it is the
[E]xaminer's position that the manipulation of the concentration of titanium
dioxide to ferric oxide respectively is obvious to one of ordinary skill in the

1 All references to the Brief (Br.) are to the “Corrected Appeal Brief,” dated
October 11, 2006.
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art in view of Fukuta's teachings, absent the showing of unexpectedness of
claimed concentration.” (Id. at 9).
We acknowledge that Aller does stand for the proposition that
“[n]ormally, it is to be expected that a change in temperature, or in
concentration, or in both, would be an unpatentable modification. Aller, 220
F.2d at 456, 105 USPQ at 235. The court in Aller also stated, however, that
“where the general conditions of a claim are disclosed in the prior art, it is
not inventive to discover the optimum or workable ranges by routine
experimentation.” Id. In this case, however, Appellants’ claimed ratio of
titanium dioxide to ferric oxide is significantly different from that disclosed
by Fukuta, and thus Fukata does not appear to teach the general conditions
of claim 1.
Moreover, there are exceptions to the rule of Aller. One such
exception is where the parameter that is optimized is not recognized to be a
result effective variable. In re Antonie, 559 F.2d 618, 620, 195 USPQ 6, 8
(CCPA 1977); In re Yates, 663 F.2d 1054, 1056, 211 USPQ 1149, 1151
(CCPA 1981); see, e.g., KSR Int’l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1742,
82 USPQ2d 1385, 1397 (2007) (“One of the ways in which a patent’s
subject matter can be proved obvious is by noting that there existed at the
time of invention a known problem for which there was an obvious solution
encompassed by the patent’s claims.”). In the case before us, we can find
nothing in Fukuta that suggests that the ratio of titanium dioxide to ferric
oxide is a result effective variable, and the Examiner also does not point to
any such teaching. Thus, there is nothing in Fukuta that suggests that it
would have been obvious to the ordinary artisan to change or optimize the
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ratio of titanium dioxide to ferric oxide from 50:1 to arrive at the claimed
ratio of 6 1/7:1 to 6 ½:1.
Claims 1-4, 6, and 9-13 stand rejected under 35 U.S.C. § 103(a) as
obvious over the combination of Miyachi and Parikh.
Miyachi is cited for the same reasons set forth above with respect to
the previous rejection (Answer 5).
Parikh teaches pharmaceutical compositions containing thiazepine, an
antidopaminergic agent, and the Examiner relies on the teaching of Parikh of
“formulating the active agent into a tablet utilizing conventional technology
and excipients.” (Answer 5.) The Examiner specifically points to Example
12, which teaches a coating composition comprising 1.85 mg of titanium
dioxide and 0.15 mg of ferric oxide (id. at 6).
The Examiner concludes:
It would have been obvious to one of ordinary skill in the
art at the time the invention was made to combine the teachings
of Miyachi and Parikh [ ] and utilize the instant excipients and
instant sustained release coating formulation when formulating
the solid dosage form of KRP-197. One would have been
motivated to look at the guidance provided by Parikh [ ] since
Parikh teaches the instant excipients and coating formulations
are conventionally utilized by . . . those skilled in art when
preparing solid dosage forms such as tablets. Therefore, it is
considered prima facie obvious for a skilled artisan to utilize
conventional excipients and coating material to prepare solid
dosage forms since they were known in the pharmaceutical art
prior to the making of the instant invention.

(Id.)
Moreover, the Examiner again relies on Aller to support the assertion
that the manipulation of the concentration of titanium dioxide to ferric oxide
is obvious to one of ordinary skill in the art.
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Appellants reiterate their arguments as to the rejection over the
combination of Miyachi and Fukuta, asserting that while Example 12
teaches a coating composition that contains both titanium dioxide and ferric
oxide, the amounts are 1.85 mg and 0.15 mg respectively, for a ratio of
1.85:0.15 or 12 ½: 1 (Br. 9).
We agree that the Examiner has failed to set forth a prima facie case
of obviousness. While the ratio taught by Parikh is closer to the claimed
ratio than the ratio taught by Fukuta, again, we can find nothing that
suggests that the ratio of titanium dioxide to ferric oxide is a result effective
variable, and the Examiner does not point to any such teaching. Thus, the
rejection is reversed for the reasons set forth above with respect to the
combination of Miyachi and Fukuta.

CONCLUSION
Because the Examiner has failed to set forth a prima facie case of
unpatentability, the rejections of record are reversed.

REVERSED

lbg

OBLON, SPIVAK, MCCLELLAND,
MAIER & NEUSTADT, P.C.
1940 DUKE STREET
ALEXANDRIA VA 22314
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