Ex Parte Kabra

Board of Patent Appeals and Interferences

Nov 24, 2009

10609975 (B.P.A.I. Nov. 24, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte BHAGWATI P. KABRA
__________

Appeal 2009-0042541
Application 10/609,975
Technology Center 1600
__________

Decided:2 November 24, 2009
__________

Before DEMETRA J. MILLS, LORA M. GREEN, and
FRANCISCO C. PRATS, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to a method of
delivering a drug to the ear. The Examiner rejected the claims as obvious.
We have jurisdiction under 35 U.S.C. § 6(b).

1 Alcon, Inc. is the real party in interest.
2 Oral argument was presented in this case on November 5, 2009.

Appeal 2009-004254
Application 10/609,975

STATEMENT OF THE CASE
Claims 12-20 stand rejected and appealed (App. Br. 5).3 Claim 12,
the only independent claim, is representative and reads as follows:
12. A method of delivering an otic drug to the ear comprising
the steps of
(a) preparing an otic composition comprising the otic drug and
a carrier, wherein the carrier comprises a low molecular weight
compound having a molecular weight of 150 - 4000, the carrier
reversibly changes from solid to liquid at a temperature of
32 - 37°C, and the low molecular weight compound has the
formula:

(I)

3 Claims 1-11 are also pending and are subject to an anticipation rejection
over Smith which has not been withdrawn (see Ans. 3; Final Rejection 2
(September 7, 2007)). As Appellant has chosen not to argue the merits of
this rejection (see App. Br. 5), we summarily affirm it. Arguments not made
are waived. See 37 C.F.R. § 41.37(c)(1)(vii) (“Any arguments or authorities
not included in the brief or a reply brief ... will be refused consideration by
the Board, unless good cause is shown.”).
Also, in view of this Board’s precedential opinion in Ex Parte
Ghuman, 88 USPQ2d 1478, 1480 (BPAI 2008) (non-appealed claims must
be canceled), when prosecution resumes in this case, the Examiner and
Appellant should work together to ensure that claims 1-11 are canceled.
In this regard, we note that Appellant had previously submitted an
Amendment After Final, which the Examiner declined to enter, attempting
to cancel claims 1-11 (see Amendment After Final 2 (filed November 2,
2007); see also Examiner’s initials and “Do Not Enter” in document entered
into electronic file on December 4, 2007).
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wherein R1 is -H, -OH, -COOH, -CnH2n+l-2m,
-COOCnH2n+l-2m, -COO(CH2CH2O)nCH2CH2OH,
-CH2R3, or

;

R2, R3 and R4 are independently -H, -OH, -COOH,
-CnH2n+l-2m, -OOCCnH2n+l-2m, -COOCnH2n+l-2m,
-COO(CH2CH2O)nCH2CH2OH,
-CnH2n+1-2mCOO(CH2CH2O)nCH2CH2OH,
-OOCCnH2n+1-2mCOOCn'H2n'+ l-2m', -COO- Na+, -COO- K+,
-SO3H, -SO3- Na+, -SO3- K+, -NH2, -Cl,

, or

;

n, n' and n" are independently 0 - 50; and
m, m' and m" are independently 0 - 10,
and

(b) inserting the composition prepared in step (a) in the ear
canal.

The Examiner cites the following documents as evidence of
unpatentability:
Aoda et al. US 4,344,968 Aug. 17, 1982
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Sawa US 5,942,508 Aug. 24, 1999
Farmer US 6,645,506 B1 Nov. 11, 2003
Smith EP 0 279 519 A1 Aug. 24, 1988

The following rejections are at issue:
(1) Claims 12, 13, and 15-20, rejected under 35 U.S.C. § 103(a) as
being unpatentable in view of Smith and Sawa (Ans. 3-4).
(2) Claim 14, rejected under 35 U.S.C. § 103(a) as being unpatentable
in view of Smith, Sawa, and Farmer (Ans. 4-5).
We reverse both of these rejections.
OBVIOUSNESS -- SMITH AND SAWA
ISSUE
The Examiner cites Example 5 of Smith as disclosing “the
composition used by the instantly claimed method,” including the drug
ibuprofen and a carrier having the formula and melting point4 recited in
claim 12 (Ans. 3). The Examiner concedes, however, that Smith “lacks a
teaching of administration of the formulation to the ear” (id.).
To meet that limitation, the Examiner cites Sawa as teaching “the use
of ibuprofen in an otic formulation, along with an antibacterial agent
(pyrinonecarboxcilic [sic] acid). Sawa teaches that the antibacterial agent is
stabilized by the addition of ibuprofen. Ibuprofen is also well known to
relieve pain, such as that that may be experienced along with infections” (id.
at 4).
Based on these teachings, the Examiner concludes that an ordinary
artisan would have considered it obvious to administer Smith’s

4 The Examiner cites Aoda as evidence that Smith’s carrier meets the
melting point limitation recited in claim 12.
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ibuprofen-containing composition to a patient’s ear “with or without the
added antibacterial. Obviousness stems from Sawa’s recognition that
ibuprofen is a useful otic active agent” (id.).
The Examiner also concludes that it would have been obvious to
include Sawa’s pyridonecarboxylic acid in Smith’s composition, because the
“combination of that agent and ibuprofen are known to be advantageous in
the art, for example, because pyri[d]onecarboxylic acid is stabilized by
ibuprofen. The artisan would further find it obvious to administer the
resulting material to the ear, because the drugs are useful when administered
by an otic route” (id.).
Appellant contends that “the facts of record show that it would not
have been prima facie obvious to a person of ordinary skill in the art at the
time of the invention to administer the (suppository) formulations of Smith
to the ear canal in view of Sawa” (App. Br. 22).
Specifically, Appellant urges, Smith’s formulations “are made to be
applied as solid dosages, such as would be consistent with the suppository
applications highlighted by the Smith reference,” whereas “Sawa relates to
solubilizing a pyridonecarboxylic acid for purposes of the production of an
aqueous solution to be used as an eye drop, nasal drop, or ear drop” (id.).
Thus, Appellant argues, “the purposes of Smith are quite different from
Sawa and their differing product forms reflect this divergence in purpose”
(id.).
Moreover, Appellant argues, Sawa was concerned with the problem of
solubilizing pyridonecarboxylic acid when used as an antibacterial whereas
“Smith does not use any pyridonecarboxylic acid and, therefore, one reading
Smith would have no reason to look to Sawa for any purpose. No problem
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is raised or addressed in Smith which would cause one skilled in the art to
look to Sawa” (id.).
In view of the positions advanced by Appellant and the Examiner, the
issue with respect to this rejection is whether Appellant has shown that the
Examiner erred in concluding that an ordinary artisan would have
considered it obvious to administer Smith’s solid ibuprofen-containing
suppository composition to a patient’s ear, based on Sawa’s disclosure that
ibuprofen is a useful solubilizing agent for producing eye, nose, or ear drops
that contain pyridonecarboxylic acids.
FINDINGS OF FACT (“FF”)
1. Smith discloses “a pharmaceutical formulation comprising a
dispersion of a pharmaceutically acceptable salt of ibuprofen in a carrier
which comprises a hydrophilic material selected from an alcohol or an ester
thereof and a polyhydric alcohol or an ester thereof” (Smith 2).
According to Smith, “when a pharmaceutically acceptable salt of
ibuprofen is employed as the active ingredient in formulations containing
this class of excipients, such formulations hav[e] advantageous storage
properties over similar formulations comprising ibuprofen itself” (id.).
2. Smith discloses that its formulations “are particularly applicable to
suppositories, topical formulations, non-aqueous liquid preparations
including syrups, sprays and injectable suspensions and to oral presentations
such as melt fill solid dosage forms and soft or hard gelatin capsules, which
may contain solid, semi-solid or liquid preparations” (id. at 3).
3. The formulation described in Example 5 of Smith contains, 32%
(w/w) ibuprofen, 5% glyceryl monostearate, and 63% glycerol esters in the
form of a product named “Suppocire B” (id. at 5).
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The formulation “was prepared by warming the glycerol esters
excipient and glyceryl monostearate to 50°C and adding the sodium salt of
ibuprofen with stirring to form a homogeneous molten mixture. The mixture
was filled into suppository cavities and allowed to cool” (id.).
4. Sawa discloses that, while pyridonecarboxylic acids are “known to be
extremely superior synthetic antibacterial agents,” they have “strikingly low
solubility in water at a physiological pH, i.e., neutral range. This imposes a
problem that an aqueous solution containing pyridonecarboxylic acid or a
pharmacologically acceptable salt thereof cannot be formulated into a
pharmaceutical preparation at a neutral pH” (Sawa, col. 1, ll. 18-26).
5. Sawa also discloses, however, that “addition of an arylcarboxylic acid
to a pyridonecarboxylic acid or a pharmacologically acceptable salt thereof
leads to successful solubilization thereof at around a physiological pH” (id.
at col. 1, ll. 63-66).
6. Sawa discloses that suitable solubilizing arylcarboxylic acids include
“pranoprofen, ibuprofen, bromfenac, 2-naphthoic acid, 2-naphthylacetic acid
and 2-naphthoxyacetic acid” (id. at col. 2, ll. 65-67 (emphasis added)).
7. Sawa discloses that one embodiment of its invention is an aqueous
solution comprising a solubilized pyridonecarboxylic acid and an
arylcarboxylic acid which can be ibuprofen (id. at col. 3, ll. 33-47).
8. Sawa discloses that “[t]he aqueous solution of the present invention is
used as an eye drop, nasal drop or ear drop” (id. at col. 9, ll. 20-21).
9. Sawa discloses that its aqueous solutions were prepared by combining
the pyridonecarboxylic acid and the solubilizing arylcarboxylic acid in
water, adjusting the solution to a neutral pH, shaking the solution for at least
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one week at 25°C, and then filtering the solution (id. at col. 9, l. 41, through
col. 10, l. 33).
10. Sawa discloses that inclusion of ibuprofen or other arylcarboxylic
acids increased the solubility of pyridonecarboxylic acids “by about 1.5-3
times” (id. at col. 10, l. 56).
11. Sawa discloses that eye drops, nasal drops, and ear drops according to
its invention were prepared, and that none of them “showed precipitation of
crystals after preservation for 4 days at room temperature” (id. at col. 10, ll.
58-60).
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. “[The Examiner]
can satisfy this burden only by showing some objective
teaching in the prior art or that knowledge generally available to
one of ordinary skill in the art would lead that individual to
combine the relevant teachings of the references.”

In re Fritch, 972 F.2d 1260, 1265 (Fed. Cir. 1992) (citations omitted,
bracketed material in original).
In KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 415 (2007), the
Supreme Court emphasized “an expansive and flexible approach” to the
obviousness question. The Court nonetheless reaffirmed that “a patent
composed of several elements is not proved obvious merely by
demonstrating that each of its elements was, independently, known in the
prior art.” Id. at 418.
Rather, as the Court stated:
[I]t can be important to identify a reason that would have
prompted a person of ordinary skill in the relevant field to
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combine the elements in the way the claimed new invention
does . . . because inventions in most, if not all, instances rely
upon building blocks long since uncovered, and claimed
discoveries almost of necessity will be combinations of what, in
some sense, is already known.

Id. at 418-419 (emphasis added); see also id. at 418 (requiring a
determination of “whether there was an apparent reason to combine the
known elements in the fashion claimed by the patent at issue”) (emphasis
added).
Ultimately, therefore, as our reviewing court has stated, “[i]n
determining whether obviousness is established by combining the teachings
of the prior art, the test is what the combined teachings of the references
would have suggested to those of ordinary skill in the art.” In re GPAC Inc.,
57 F.3d 1573, 1581 (Fed. Cir. 1995) (internal quotations omitted).
When evaluating claims for obviousness, “the prior art as a whole
must be considered. The teachings are to be viewed as they would have
been viewed by one of ordinary skill.” In re Hedges, 783 F.2d 1038, 1041
(Fed. Cir. 1986).
ANALYSIS
We agree with Appellant that the Examiner failed to make a prima
facie case that an ordinary artisan would have considered it obvious to
administer Smith’s solid ibuprofen-containing suppository composition to a
patient’s ear, based on Sawa’s disclosure that ibuprofen is a useful
solubilizing agent for producing eye, nose, or ear drops that contain
pyridonecarboxylic acids.
We acknowledge that Smith’s solid formulation contains ibuprofen, a
drug disclosed by Sawa as being useful in compositions administered to the
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ear. However, we do not agree that Sawa’s disclosure of administering ear
drops, which are liquid at room temperature, would have suggested to an
ordinary artisan that it would be desirable, or even suitable, to modify
Sawa’s teachings and administer its active agents in the form of a solid
composition normally used as a suppository. Nor has the Examiner pointed
to anything specific in the prior art, or in the knowledge available to a person
of ordinary skill, suggesting that an ordinary artisan seeking to administer
medication to a patient’s ear would have considered a solid suppository-type
dosage form to be equivalent to ear drops.
Rather, viewing the prior art as a whole, the Sawa reference would
have suggested to an ordinary artisan that ibuprofen was useful for
solubilizing pyridonecarboxylic acid in antibacterial solutions administered
to the ear, the solutions being liquid at room temperature. In contrast, Smith
would have suggested to an ordinary artisan that a solid formulation
containing ibuprofen and a glyceryl monostearate/glycerol ester excipient
was useful as a suppository.
Given the different forms, liquid versus solid, and the divergent uses
disclosed for these two dosage formulation, we are not persuaded that an
ordinary artisan viewing these references would have been prompted to
insert Smith’s suppository composition into a patient’s ear, rather than
simply use Sawa’s aqueous solution which was specifically formulated for
ear administration.
Accordingly, we agree with Appellant that the Examiner erred in
concluding that an ordinary artisan would have considered it obvious, in
view of the cited references, to perform claim 12’s step of inserting a
composition having the claimed properties, into the ear canal. We therefore
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reverse the Examiner’s rejection of claim 12, and its dependent claims 13,
and 15-20, as being obvious over Smith and Sawa.
OBVIOUSNESS -- SMITH, SAWA, AND FARMER
Claim 14 stands rejected under § 103(a) as being obvious in view of
Smith, Sawa, and Farmer (Ans. 4-5). Claim 14 depends from claim 12
through claim 13.
Claims 13 and 14 read as follows:
13. The method of Claim 12 wherein the composition
prepared in step (a) is dropped, injected, deposited, or sprayed
into the external ear.

14. The method of Claim 13 wherein the composition
prepared in step (a) is warmed to a temperature above 32 °C
and administered topically or locally as an ear drop or through a
cannula.

The Examiner concedes that Smith and Sawa do not disclose using an
ear-dropper to administer Smith’s composition, and to meet that limitation,
cites Farmer as disclosing that it is common practice to use an ear-dropper to
administer drugs to the ear (Ans. 4). Based on the references’ combined
teachings, the Examiner concludes:
It would have been prima facie obvious to a person of
ordinary skill in the art at the time of the invention to use an ear
dropper and to warm the composition, as taught by Farmer.
The motivation to use the ear dropper is to place the
composition accurately in the ear, as Farmer suggests. The
motivation to warm the composition comes from the teaching to
use warm water to remove excess medicament. In this context,
“warm” is understood to mean above 32 C (90 F). The
composition, after inserted in the ear, is warmed by the washing
step which also removes excess medicament, as taught by
Farmer.
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(Id. at 5.)
We reverse this rejection as well. The Examiner points to no teaching
in Farmer that remedies the deficiencies, discussed above, with respect to the
combination of Smith and Sawa. While it might be common to use an ear-
dropper to administer ear-targeted formulations, the Examiner has not
provided any logical or art-specific reason why an ordinary artisan, rather
than simply administering Sawa’s formulation, would go to the trouble of
creating a solid formulation like Smith’s, and then heat it for administration.
Thus, we agree with Appellant that the Examiner erred in concluding
that claim 14 would have been obvious to an ordinary artisan. We therefore
reverse the Examiner’s obviousness rejection of that claim over Smith,
Sawa, and Farmer.

SUMMARY
As noted above, we summarily affirm the Examiner’s rejection of
claims 1-11 as anticipated by Smith, in view of Appellant’s failure to argue
the merits of this rejection.
However, for the reasons discussed above, we reverse the Examiner’s
rejection of claims 12, 13, and 15-20, under 35 U.S.C. § 103(a) as being
unpatentable in view of Smith and Sawa, and also reverse the rejection of
claim 14 under § 103(a) as being obvious in view of Smith, Sawa, and
Farmer.
AFFIRMED-IN-PART

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cdc

ALCON RESEARCH, LTD.
PATRICK M. RYAN(Q-148)
R&D COUNSEL
6021 SO. FREEWAY
FORT WORTH TX 76134-2099
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