Ex Parte Miura et al

Patent Trial and Appeal Board

Jun 13, 2013

12067722 (P.T.A.B. Jun. 13, 2013)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte HIROSHI MIURA and MAKOTO KANEBAKO
__________

Appeal 2011-010580
Application 12/067,722
Technology Center 1600
__________

Before FRANCISCO C. PRATS, ULRIKE W. JENKS, and JOHN G. NEW,
Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL
This appeal1 under 35 U.S.C. § 134 involves claims to indomethacin
compositions. The Examiner entered two rejections for obviousness.
We have jurisdiction under 35 U.S.C. § 6(b). We affirm-in-part.
STATEMENT OF THE CASE
The Specification discloses that “when liquid preparations containing
both indomethacin and a sulfite are stored at a low temperature, crystals are
precipitated with time” (Spec. 2). Thus, the Specification discloses, “there
have been demanded indomethacin-containing external liquid preparations

1 Kowa Co., Ltd. is the real party in interest (App. Br. 2).
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which provide good feeling of use, which exhibit high percutaneous
absorption of the active ingredient, and which do not produce precipitated
crystals with time particularly in a low-temperature environment” (id. at 3).
To address this issue, Appellants “performed extensive studies . . .,
and have quite unexpectedly found that when polyethylene glycol having an
average molecular weight of 3,000 to 15,000 is added to a preparation
containing indomethacin, a lower alcohol, water, and a sulfite, crystal
precipitation is effectively prevented particularly in a low-temperature
environment” (id. at 4).
Claims 1-19 stand rejected and appealed (see App. Br. 4). Claims 1
and 6, the independent claims, illustrate the appealed subject matter and read
as follows:2
1. An external liquid preparation comprising:
indomethacin,
a lower alcohol,
water,
a sulfite that is sodium bisulfite or sodium pyrosulfite (sodium
metabisulfite), and
polyethylene glycol having an average molecular weight of 3,000 to
15,000.

6. A composition comprising:
indomethacin,
a lower alcohol,
water,
a sulfite that is sodium bisulfite or sodium pyrosulfite (sodium
metabisulfite), and

2 The Examiner states that the after-final amendment filed November 22,
2010 was entered (see Ans. 2-3). The version of the claims at pages 25-27
of the Appeal Brief is therefore before us for review.
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polyethylene glycol having an average molecular weight of 3,000 to
15,000.

The following rejections are before us for review:
(1) Claims 1-19, under 35 U.S.C. § 103(a) as obvious over Shirai,3
Kibbe,4 and the Columbia Encyclopedia Online5 (Ans. 4); and
(2) Claims 1, 2, and 4-16, under 35 U.S.C. § 103(a) as obvious over
Asche,6 Yamahira,7 and the Columbia Encyclopedia Online (Ans. 7-11).
OBVIOUSNESS –
SHIRAI, KIBBE, AND THE COLUMBIA ENCYCLOPEDIA
The Examiner cited Shirai as disclosing external use indomethacin
compositions containing all of the ingredients in the compositions recited in
Appellants’ claims (see Ans. 4-5). The Examiner cited the Columbia
Encyclopedia’s definition of “liquid” as evidence that Shirai’s “‘gel cream’”
compositions would be considered liquids as required by Appellants’ claim
1, noting in particular that Shirai’s compositions included from 89 to 91.7%
liquid ingredients (id. at 5).
The Examiner conceded that Shirai’s compositions differed from the
claimed compositions in that the polyethylene glycol (PEG) in Shirai’s
exemplified compositions had an average molecular weight of 400, outside

3 WO 2004/010994 A1 (published May 2, 2004). The Examiner cites to
U.S. Patent App. Pub. No 2005/0239868 (published Oct. 27, 2005) as the
English language equivalent of Shirai, and we do the same.
4 HANDBOOK OF PHARMACEUTICAL EXCIPIENTS 392-419 (monograph for
polyethylene glycol) (Arthur H. Kibbe ed., 3d. ed. 2000).
5 COLUMBIA ENCYCLOPEDIA (6th ed. Online) definition for “liquid”
(http://www.encyclopedia.com/topic/liquid.aspx), accessed August 22, 2009.
6 U.S. Patent No. 4,917,886 (issued April 17, 1990).
7 JP 59-088419 (published May 22, 1984).
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the range of 3,000 to 15,000 recited in Appellants’ independent claims 1 and
6 (see id. at 5-6).
To address that deficiency, the Examiner cited Kibbe as evidence that
an ordinary artisan would have recognized that PEG within the claimed
average molecular weight range was suitable for use in topical compositions
(see id. at 6). In particular, the Examiner found that Kibbe taught that PEG
with molecular weights above 1,000 were solid at room temperature, and
that “grades of polyethylene glycol of 6000 and above are available as easy-
to-use free-flowing milled powders unlike the odorous viscous liquids,
pastes and waxes seen at the lower grades” (id.).
Based on the references’ combined teachings, the Examiner
concluded that an ordinary artisan would have considered it obvious to
“formulate indomethacin external preparations comprising 1% polyethylene
glycol 400 as taught by Shirai, utilizing the polyethylene glycols taught by
Kibbe, particularly those that are easiest to handle, e.g., grade 6000” (id. at
6-7). In particular, the Examiner found that one skilled in the art would have
“reasonably expected success from this combination due to the general
teaching in Shirai that one could utilize a polyethylene glycol as a wetting
agent in formulating the indomethacin external preparations and the teaching
in Kibbe that the solid grades of polyethylene glycols are generally
employed in topical preparations” (id. at 7).
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[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.
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Appellants’ arguments do not persuade us that the preponderance of
the evidence fails to support the Examiner’s prima facie case of obviousness.
As discussed below, however, we agree with Appellants that the evidence of
unexpected results outweighs the evidence of prima facie obviousness as to
claims 1-5.
As to the prima facie case, as the Examiner found, and Appellants do
not dispute, Shirai exemplifies compositions containing all of the claimed
ingredients, except that the PEG in the exemplified compositions has a
molecular weight of 400 (see Shirai [0036]- [0061] (Examples 1-5)). As the
Examiner also found, however, Shirai provides a general teaching of the
usefulness of PEG in its compositions (id. at [0033] (“Further, as the wetting
agent, polyhydric alcohols such as glycerin, ethylene glycol, propylene
glycol, oleyl alcohol, 1,3-butylene glycol, isopropylene glycol, polyethylene
gylcol [sic], and the like can be given.”) (Emphasis added)).
Moreover, as the Examiner further found, Kibbe discloses that PEGs
within the claimed molecular weight range are solids at room temperature
(see Kibbe 393), and further teaches the suitability of solid grades of PEG in
topically applied compositions:
Polyethylene glycols are stable, hydrophilic substances
that are essentially nonirritant to the skin . . . . Although they
do not readily penetrate the skin, polyethylene glycols are water
soluble and as such are easily removed from the skin by
washing; they are therefore useful as ointment bases. Solid
grades are generally employed in topical ointments with the
consistency of the base being adjusted by the addition of liquid
grades of polyethylene glycol.

(Id. at 392.)
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Given Shirai’s disclosure that PEG, without any molecular weight
limitation, was desirable in its compositions, and further given Kibbe’s
disclosure of the general applicability of solid grades of PEG in topical
compositions, including PEG within the molecular weight range recited in
claims 1 and 6, Appellants’ arguments questioning motivation (see App. Br.
14-15; see also Reply Br. 1-3) do not persuade us that the Examiner erred in
finding that an ordinary artisan would have been prompted to include PEG
of the claimed molecular weight in Shirai’s compositions.
It may be true, as Appellants argue (see App. Br. 13-14), that the
references would have suggested including the claimed PEG in Shirai’s
compositions for a different reason than Appellants’ express purpose of
eliminating crystal precipitation.
As the Supreme Court has pointed out, however, claims are properly
considered obvious when the prior art suggests practicing subject matter
encompassed by the claims, even when the prior art’s rationale is different
than the patent applicant’s. KSR Int’l v. Teleflex Inc., 550 U.S. 398, 419
(2007) (“In determining whether the subject matter of a patent claim is
obvious, neither the particular motivation nor the avowed purpose of the
patentee controls. What matters is the objective reach of the claim. If the
claim extends to what is obvious, it is invalid under § 103.”).
Thus, given the references’ teachings, Appellants’ arguments do not
persuade us that a preponderance of the evidence fails to support the
Examiner’s prima facie case of obviousness. We do agree with Appellants,
however, that their evidence of unexpected results is sufficient to outweigh
the evidence of prima facie obviousness.
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Specifically, as Appellants point out, and as presented in the
Specification, PEG within the claimed molecular weight range eliminates
crystal precipitation in indomethacin compositions stored in the cold,
whereas PEG of molecular weights above and below the claimed range do
not eliminate crystal precipitation (see Spec. 12-13 (Table 1 and explanatory
text)).
As our reviewing court has explained, “[m]ere improvement in
properties does not always suffice to show unexpected results. . . .
[However,] when an applicant demonstrates substantially improved results .
. . and states that the results were unexpected, this should suffice to establish
unexpected results in the absence of evidence to the contrary.” In re Soni,
54 F.3d 746, 751 (Fed. Cir. 1995).
The Examiner does not direct us to, nor do we discern, any clear or
specific evidence suggesting that including PEG of the claimed molecular
weight range would eliminate crystal precipitation, as demonstrated in
Appellants’ Specification. Nor does the Examiner direct us to any
disclosure in any of the cited references suggesting that optimizing PEG
grades through routine experimentation would eliminate crystal
precipitation.
While the Examiner urges that eliminating crystal precipitation would
inherently result from selecting PEG of the claimed molecular weight, the
Examiner directs us to no evidence suggesting that the claimed PEG had
been included in a composition containing the other ingredients recited in
Appellants’ claims. As Appellants point out, the cases cited by the
Examiner (Ans. 13), In re Spada, 911 F.2d 705 (Fed. Cir. 1990), and Atlas
Powder Co. v. Ireco, Inc., 190 F.3d 1342 (Fed. Cir. 1999), explain principles
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of inherency where a prior art composition anticipates a claimed
composition, a situation not present here.
The Examiner argues that only claims 3 and 17-19 are commensurate
in scope with Appellants’ evidence of unexpected results as only those
claims limit the PEG concentration to concentrations comparable to that
used in Appellants’ experiments (see Ans. 15).
As claim 6 and its dependents are not limited to liquid compositions,
and as Appellants’ unexpected results are limited to eliminating crystal
precipitation from liquid indomethacin compositions, we agree with the
Examiner that claim 6 and its dependents are not commensurate in scope
with the evidence of unexpected results. We therefore affirm the
Examiner’s rejection of claim 6 and its dependents over Shirai, Kibbe, and
the Columbia Encyclopedia.
As to the liquid compositions of claim 1 and its dependents, however,
we find that Appellants’ evidence of unexpected results is sufficiently
commensurate in scope with the claimed subject matter so as to outweigh
the evidence of prima facie obviousness advanced by the Examiner.
As our reviewing court has explained, it is well settled that
“[e]vidence of secondary considerations must be reasonably commensurate
with the scope of the claims. . . . This does not mean that an applicant is
required to test every embodiment within the scope of his or her claims.” In
re Kao, 639 F.3d 1057, 1068 (Fed. Cir. 2011). Rather, “[i]f 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 scope of the claims.” Id.
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Thus, to demonstrate that a product, such as a chemical compound,
has unexpected properties sufficient to overcome a prima facie showing of
obviousness, a patent applicant need not “produce superior results in every
environment in which the compound may be used. To be patentable, a
compound need not excel over prior art compounds in all common
properties.” In re Chupp, 816 F.2d 643, 646 (Fed. Cir. 1987). Instead,
“[e]vidence that a compound is unexpectedly superior in one of a spectrum
of common properties, as here, can be enough to rebut a prima facie case of
obviousness.” Id.
Thus, as we find that the evidence of unexpected results is sufficiently
commensurate in scope with claim 1 so as to outweigh the evidence of prima
facie obviousness, we reverse the Examiner’s rejection of claim 1, and its
dependents, as obvious over Shirai, Kibbe, and the Columbia Encyclopedia.
OBVIOUSNESS –
ASCHE, YAMAHIRA, AND THE COLUMBIA ENCYCLOPEDIA
In the second rejection, the Examiner found that Asche exemplified an
indomethacin-containing composition that also contained the alcohol, water,
and PEG required by Appellants’ claims 1 and 6 (see Ans. 9). Similar to the
rejection discussed above, the Examiner relied on the Columbia
Encyclopedia as evidence that Asche’s compositions would be considered
liquids, as required by Appellants’ claim 1.
The Examiner conceded that Asche’s exemplified composition
differed from Appellants’ claimed compositions in that Asche’s composition
did not contain a sulfite, and also in that Asche’s exemplified composition
had a PEG with a lower molecular weight than required by the claims (see
id.). The Examiner noted, however, that Asche taught the suitability of
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sulfite stabilizers in its compositions (see id. at 8), and further noted that
Asche included a broad teaching regarding the range of suitable molecular
weights of the PEG in its compositions, which overlapped the claimed range
(see id. at 7-8).
The Examiner reasoned that, “[a]lthough Asche does not teach a
single embodiment reading on the claims, the Asche patent teaches each of
the limitations present in the instant claims” (id. at 11). Therefore, the
Examiner concluded, an ordinary artisan would have considered it obvious
“to formulate indomethacin-containing external preparations comprising a
lower alcohol, water, a sulfite, e.g., sodium bisulfite, and a polyethylene
glycol having an average molecular weight of 3,000 to 15,000, such that the
mass % and mass ratios read on those recited by the instant claims” (id.).
As with the rejection discussed above, Appellants’ arguments do not
persuade us that the preponderance of the evidence fails to support the
Examiner’s prima facie case of obviousness. As discussed below, however,
we again agree with Appellants that the evidence of unexpected results
outweighs the evidence of prima facie obviousness as to claims 1-5.
It is undisputed that Example 6 of Asche discloses a composition that
contains indomethacin, alcohol, water, and PEG. As the Examiner found,
however, Asche also discloses the suitability of sulfite stabilizers in its
compositions (Asche, col. 8, ll. 35-45). We therefore agree with the
Examiner that an ordinary artisan would have been prompted to include the
claimed bisulfites in Asche’s indomethacin composition.
As to PEG, Asche describes its use as a co-solvent in the disclosed
topical compositions, so as to “maintain the active ingredient left behind on
the skin in solution” (id. at col. 3, ll. 66-67). Thus, while the PEG in
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Asche’s Example 6 undisputedly has a molecular weight of 1500, as the
Examiner found, and Appellants concede, Asche describes suitable PEGs as
those “having a chain length of from approximately 200 to approximately
6000, preferably from approximately 300 to approximately 1500, units” (id.
at col. 4, ll. 5-7).
Appellants find, and the Examiner does not dispute, that Asche’s
broader range corresponds to a molecular weight range of 8,862 to 264,062
for Asche’s PEG (App. Br. 18). It is thus also undisputed that the molecular
weight range of PEG described in Asche as being suitable in its
compositions overlaps the claimed range.
As our reviewing court has stated, “[i]n cases involving overlapping
ranges, we and our predecessor court have consistently held that even a
slight overlap in range establishes a prima facie case of obviousness.” In re
Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003). Moreover, “a prima facie
case of obviousness exists when the claimed range and the prior art range do
not overlap but are close enough such that one skilled in the art would have
expected them to have the same properties.” Id.
While it may be true that the overlap between the claimed and prior
art PEG molecular weight ranges is a relatively small portion of Asche’s
total range (see App. Br. 18; see also Reply Br. 3-4), Appellants point to no
clear or specific evidence of record suggesting that an ordinary artisan would
have failed to consider PEG of the claimed molecular weight suitable in
Asche’s compositions. Nor have Appellants pointed to any evidence in the
prior art suggesting that PEG within the claimed molecular weight range
would have been expected to have properties significantly different from
other PEGs within the molecular weight range described in Asche.
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We acknowledge, as Appellants argue (see App. Br. 19), that Asche
includes a narrower range of PEG of 300 to 1500 units (see Asche, col. 4, ll.
6-7).
We are not persuaded that this narrower range would have taught
away from using PEGs encompassed by the claimed range. In particular,
Appellants have not adequately explained why the narrower range in Asche
would fail to overlap or abut the claimed molecular weight range of PEGs,
given Appellants’ method of calculating PEG molecular weights.
Moreover, it is well settled that “in a section 103 inquiry, ‘the fact that
a specific [embodiment] is taught to be preferred is not controlling, since all
disclosures of the prior art, including unpreferred embodiments, must be
considered.’” Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804,
807 (Fed. Cir. 1989) (quoting In re Lamberti, 545 F.2d 747, 750 (CCPA
1976)); see also In re Mills, 470 F.2d 649, 651 (CCPA 1972) (“All the
disclosures in a reference must be evaluated, including nonpreferred
embodiments, and a reference is not limited to the disclosure of specific
working examples.” (Citations omitted).)
Further, for the reasons discussed above, the fact that Appellants’
purpose in selecting the claimed molecular weight range of PEG might differ
from Asche’s reason does not persuade us that an ordinary artisan lacked
motivation for using PEG within the claimed range in Asche’s compositions.
See KSR, 550 U.S. at 419 (“In determining whether the subject matter of a
patent claim is obvious, neither the particular motivation nor the avowed
purpose of the patentee controls.”).
In sum, for the reasons discussed, we are not persuaded that the
preponderance of the evidence fails to support the Examiner’s prima facie
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case of obviousness. As discussed above, however, we do agree with
Appellants that the evidence of unexpected results is sufficient to outweigh
the evidence of prima facie obviousness as to claims 1-5, which are directed
to liquid compositions. We therefore reverse the Examiner’s obviousness
rejection of claims 1-5 over Asche, Yamahira, and the Columbia
Encyclopedia Online.
However, as claim 6 and its dependents are not directed to liquid
compositions, we agree with the Examiner that those claims are not
commensurate in scope with Appellants’ showing of unexpectedness. We
therefore affirm the Examiner’s rejection of claims 6-19 as obvious over
Asche, Yamahira, and the Columbia Encyclopedia Online.

SUMMARY
We reverse the Examiner’s obviousness rejection of claims 1-5 over
Shirai, Kibbe, and the Columbia Encyclopedia Online.
However, we affirm the Examiner’s rejection of claims 6-19 as
obvious over Shirai, Kibbe, and the Columbia Encyclopedia Online.
We reverse the Examiner’s obviousness rejection of claims 1, 2, 4,
and 5 over Asche, Yamahira, and the Columbia Encyclopedia Online.
However, we affirm the Examiner’s rejection of claims 6-19 as
obvious over Asche, Yamahira, and the Columbia Encyclopedia Online.

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TIME PERIOD
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-IN-PART

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