Ex Parte Krishnamoorthy

Patent Trial and Appeal Board

Jun 28, 2016

12584186 (P.T.A.B. Jun. 28, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/584, 186 0910112009
23702 7590 06/30/2016
Bausch & Lomb Incorporated
1400 North Goodman Street
Rochester, NY 14609
FIRST NAMED INVENTOR
Ramesh Krishnamoorthy
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www .uspto.gov
ATTORNEY DOCKET NO. CONFIRMATION NO.
P03359C2 6684
EXAMINER
FAY,ZOHREHA
ART UNIT PAPER NUMBER
1621
NOTIFICATION DATE DELIVERY MODE
06/30/2016 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address( es):
patents@bausch.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
Ex parte RAMESH KRISHNAMOORTHY
Appeal2013-006310 1
Application 12/584,1862
Technology Center 1600
Before FRANCISCO C. PRATS, MELANIE L. McCOLLUM, and
ULRIKE W. JENKS, Administrative Patent Judges.
PRATS, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to a method of
stabilizing the pH of a pharmaceutical composition. The Examiner rejected
the claims as obvious.
We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
1 Bausch & Lomb, Inc., is the real party in interest (App. Br. 3).
2 This application is a continuation of Application No. 10/698,322, in which
a similar rejection was affirmed in a decision in Appeal No. 2010-001044,
and reaffirmed on rehearing. App. Br. 3; see also App. Br., Related
Proceedings Appendix (includes copies of previous decisions on appeal and
rehearing).
Appeal2013-006310
Application 12/584, 186
STATEMENT OF THE CASE
The sole rejection before us for review is the Examiner's rejection of
claims 14, 15, and 25-30 under 35 U.S.C. § 103(a) as being obvious in view
of Guy,3 Amselem,4 and the Physicians' Desk Reference ("PDR"). 5 Final
Action 2-5.
Appellant does not contest the rejection as to claims 14, 15, and 25-
27. See App. Br. 3 ("Claims 14, 15 and 25-27 are pending, but are not
subject to this Appeal.").
Accordingly, we summarily affirm the Examiner's rejection as to
claims 14, 15, and 25-27. See MPEP § 1205.02 (Arguments and evidence
not presented in an appeal brief "are waived for purposes of the appeal and
the Board may summarily sustain any grounds of rejections not argued.");
see also 37 C.F.R. § 41.31(c) ("An appeal, when taken, is presumed to be
taken from the rejection of all claims under rejection unless cancelled by an
amendment filed by the applicant and entered by the Office.").
Claims 28-30, therefore, remain for consideration on the merits.
Claims 28 and 29 are representative of those claims and read as follows
(App. Br., Claims Appendix ii; paragraphing added):
28. A method of stabilizing the pH of a pharmaceutically
acceptable, aqueous suspension comprising Loteprednol
etabonate in which a buff er system is not present in the
suspension, the method comprising:
stabilizing for extended periods of storage the buffer
system free aqueous suspension comprising from 4.3 mg/mL to
3 Guy et al., U.S. Patent No. 5,540,930 (issued July 30, 1996).
4 Amselem et al., U.S. Patent No. 5,747,061 (issued May 5, 1998).
5 Physicians' Desk Reference for Ophthalmic Medicines, p. 218, 30th Edition
(2002).
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Application 12/584, 186
5.3 mg/mL of the Loteprednol etabonate by adding a pH
stabilizing amount of tobramycin to the suspension,
wherein the stabilizing is demonstrated by a smaller
change in pH as compared to a similar suspension in the
absence of the tobramycin, the pH of the suspension stabilized
by a factor of about 5.1 to about 5.4 over the similar suspension
absent tobramycin, as measured over six months of storage at
40°C.
29. The method of claim 28 wherein the aqueous
suspension comprises 0.5 wt.% Loteprednol etabonate and 0.3
wt.% tobramycin.
OBVIOUSNESS
FINDINGS OF FACT ("FF'')
1. Guy discloses "aqueous suspensions of soft corticosteroids such as
loteprednol etabonate [LE] suitable for therapeutic use in the eye, ear, or
nose. The aqueous suspensions of LE are surprisingly stable and can remain
in a state suitable for immediate suspension when desired, even after
extended periods of settling." Guy, col. 3, 11. 2-7; see also Amselem, col. 3,
11. 5-10 (substantially same disclosure).
Guy discloses that the loteprednol etabonate is included at "a final
concentration in the suspension of about 0.2-2.0%, preferably about 0.5-
1.0% (w/w)." Guy, col. 3, 11. 17-19; see also Amselem, col. 3, 11. 27-31
(disclosing loteprednol etabonate at concentrations "Oto about 2% by
weight, more preferably about 0.1-1 % by weight and most preferably about
0.05---0.5% by weight").
2. Guy discloses that its suspensions "are prepared by thoroughly mixing
the drug (component (A)), suspending agent (component (B)), and surface
active agent (component (C)). Optionally, tonicity agents (component (D))
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Application 12/584, 186
and preservatives (component (E)) may be included." Guy, col. 3, 11. 63---67;
see also Amselem, col. 4, 11. 6-10 (substantially same disclosure).
3. Guy discloses that, as drug component (A), preferably "soft steroids,
most preferably LE [loteprednol etabonate], can be employed. Also other
steroids such as beclomethasone, betamethasone, fluocinolone,
fluorometholone, exednisolone, may be employed." Guy, col. 4, 11. 1-7; see
also Amselem, col 4, 11. 11-14 (substantially same disclosure).
4. Guy discloses that its suspensions can also contain "additional
therapeutic drugs such as drugs for treating glaucoma, anti-inflammatory
drugs, antibiotic drugs, anti-cancer drugs, anti-fungal drugs and anti-viral
drugs. . . . Additional therapeutic materials which may be employed include
but are not limited to tobramycin, gentamycin or other antibiotics." Guy,
col. 4, 11. 41-54 (emphasis added); see also Amselem, col. 5, 11. 1-13
(substantially same disclosure).
5. The PDR discloses an "antibiotic and steroid combination" named
"TOBRADEX®," which contains 0.3% tobramycin and 0.1 %
dexamethasone. PDR 218.
Benzalkonium chloride is listed as the lone preservative ingredient,
and the following ingredients are listed as "[i]nactives: Tyloxapol, Edetate
Disodium, Sodium Chloride, Hydroxyethyl Cellulose, Sodium Sulfate,
Sulfuric Acid and/or Sodium Hydroxide (to adjust pH) and Purified Water."
Id.
6. The PDR discloses that the "use of a combination drug with an anti-
infective component is indicated where the risk of superficial ocular
infection is high or where there is an expectation that potentially dangerous
number of bacteria will be present in the eye." Id.
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Application 12/584, 186
7. The Specification discloses that it has "surprisingly been discovered
that the aminoglycoside tobramycin, when present in a pH stabilizing
amount, helps to stabilize loteprednol etabonate containing formulations
over time to provide better storage characteristics." Spec.3.
8. The Specification discloses that a "study was undertaken to compare a
standard LE-tobramycin composition having different concentrations of
Povidone and different types of Povidone. The example compositions also
contained standard pharmaceutical components. Examples III and VI were
used as controls (no tobramycin) to observe the effect of tobramycin on the
pH of the composition." Id. at 8.
5
Appeal2013-006310
Application 12/584, 186
The following table, presented at page 10 of the Specification, provides
results from the described study:
STABlLiTY Of LE,·TOBRAMYCfN MATRJX (w~tt~ d~ffuren~ vi8t:mdy)
··································-y1n;~·-······················y;'.iiifa:·····················n:. ----------------------·---···-·''"""··-w.·-;i
""'""'"""""""""""'J~tt!S'!tt!~L""'"""""'U1~!&~~!1tL""""""'"Q~"\lit pH •
I 0 3. l!l 4.9H:i fi.49 •
IU\% l 3.1:5 '"' 623 I
I PVf'·C3(1 2 HW! 5.(10~ 6.tf.."i I
I ~ :HJ:% 5.06')' 5.95 """"""'j
I n o :~.His 5.:!41 6.47 ',!
I L:'l% :HJl9 6..2!
I Pvr.un 2 2 §l s rn 5 .. S9
I 3 5.J7 Ii
-~-----------------------------------------·--·-·"""""""""""""""""""""""""""""""""""""'----~-<
m o ssui
pyp.f'.Jf)
Cimhd J
6
5 411
$.AH
~--~---------~-----~·•••••--••.-w""""""""'"
(l l2Q{j
't9<1
6.fl
(>.47
(l.l.)
s,.r1 (t.21
6 J2J2 :rrm (;_o~n
~--~-~""'""~""~~-~~~-~---'--'-'---....,;
n 1.~SH2
2~3R8
2 204
::i: 2.82
4J2
4.2M
(i.6l
(>JS
6.:n
6J4
6 2.1{n 4.:uo 6JM
.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.---.-.-------.-------.-.-.--.-.-.-.--.--.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.-.- -------------------------------------------------------------------------------. ...................................... ........
@~:_ ~ _i_J]t_ I
The table shows the results of pH stability testing "of various
compositions having differing viscosity. PVP-C30 is Povidone having a
molecular weight of around 30,000 and PVP-K90 is Povidone having a
molecular weight of around 90,000 .... In general a pH between 4.5 and 7.0
is considered acceptable for pharmaceutical ophthalmologic use of these
compositions." Spec. 12-13.
6
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The Specification states that the data "demonstrates that compositions
of the present invention having tobramycin display a more gradual decrease
in pH over time and less of a total change in pH over time as compared to
similar compositions which do not contain tobramycin." Id. at 13.
9. Appellant's Table 6 is reproduced below
TABLE6
STA.BIUTY OF LE-TOBRA.;\ilYCIN MATRLX
Ex. I Tocb. TO 2 Week 4 Week ~ 7Wcd~ 9 Week i
·········· !(ni!i'm1) lrH ------ ............................................. - ........................................... ......,...,..,..,...... ........................ "' ~iioo;c ·-~o;c---=~~~~~c I 40"'C 25"C 40"C 25"'C 2.S"C ___ ..., _____________ ................................ ............................ _ -. ....................
Ex ... 2 l ~6.61 6.425 6.553 6.362 6.S3 l l6.l29 6.460 .f).{}6 l 6.J9& I
,...,_ .......................................... .
Ex.3 (I" ,_1 6.63 S.867 6.328 5.681 6.083 (5.273 6.018 5.146:
Ex.4 0.1 6.40 5.32 6.005 4.864 15.672 j4.5M 5.422 4.429
........................ ..................
j4.369 Ex. 5 tl03 16.48 SJS3 6.091 4.589 S,646 5.438 4.275 -----+--·
{i.6Q SAM ::?..!.~----~~~-~- 14.548 5.745 4375 Ex. 6 iO 5.984 .................... .............................................
Regarding Table 6, the Specification states:
As the data show, the composition of Example 2 having a
pH of 6.61 at TO and containing 1 mg/ml of tobramycin
displayed a more gradual decrease in pH over time and less of a
total change in pH over time as compared to the composition of
Example 6 having a pH of 6.60 at TO and containing no
tobramycin and the compositions of Examples 3-5 containing
0.3 mg/ml, 0.1 mg/ml and 0.03 mg/ml of tobramycin,
respectively. This clearly shows that there is a critical lower
limit in the amount of tobramycin necessary to be effective to
stabilize the pH of the composition which is buffer free.
Therefore, the data show that a certain amount of tobramycin is
effective to provide a composition having a longer shelf life
during storage.
Id. at 15.
7
i 15.942 i
jS.300
ls.234
i~:623 .
Appeal2013-006310
Application 12/584, 186
DISCUSSION
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden . . . of presenting a
primafacie case ofunpatentability ....
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.
In the instant case, Appellant argues the claims subject to the rejection
in two groups: (1) a first group including claim 28 only, and (2) a second
group containing claims 29 and 30. App. Br. 5.
Appellant's arguments do not persuade us that the Examiner failed to
make a prima facie case of obviousness as to claims 28 and 29, nor are we
persuaded that the Examiner erred in finding that Appellant's evidence of
unexpected results was insufficient to overcome the prima facie case.
As an initial matter, as noted above, this application is a continuation
of Application No. 10/698,322, in which a similar rejection was affirmed in
a decision in Appeal No. 2010-001044, and reaffirmed on rehearing. App.
Br. 3; see also App. Br., Related Proceedings Appendix (includes copies of
previous decision on appeal and rehearing, hereinafter referred to as "the
'322 Appeal Decision" and "the '322 Rehearing Decision").
As Appellant explains (App. Br. 3), on rehearing in the previous
appeal, Appellant presented argument regarding In re Shetty, 566 F.2d 81
(CCPA 1977). See the '322 Rehearing Decision at 2. Because that line of
argument had not been presented previously, we declined to address it on
rehearing. Id. at 3. We address Appellant's arguments regarding Shetty
herein below.
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Application 12/584, 186
As a second initial matter, Appellant presents a series of seven
Findings of Fact. App. Br. 5---6. It is unclear, however, whether the
Findings of Fact are intended to be points of argument, which we are
requested to address separately from Appellant's substantive argument
regarding the Examiner's rejection. In any event, as to Appellant's assertion
that the presence of sodium sulfate and sulfuric acid in the Tobradex®
composition described in the PDR "provide[ s] a buffer system to stabilize
the pH of the pharmaceutical formulation" (App. Br. 6), as discussed in the
'322 Appeal Decision, Appellant has not presented any clear or specific
evidence to support that assertion. See '322 Appeal Decision at 12.
As to the merits of the Examiner's rejection, claim 28 recites a
method of stabilizing the pH of a pharmaceutically acceptable aqueous
suspension that includes loteprednol etabonate, at a concentration of from
4.3 mg/mL to 5.3 mg/mL, but does not include a buffer system. App. Br.,
Claims Appendix ii. Claim 29 further limits the loteprednol etabonate
concentration to 0.5 weight percent. Id.
The sole process step required by claim 28 is the step of stabilizing
the buffer-free suspension, for extend periods of storage, by adding a pH
stabilizing amount of tobramycin to the suspension. Id. Claim 28 provides
that stabilizing is demonstrated by a smaller change in pH as compared to a
similar suspension in the absence of the tobramycin. Id.
Claim 28 requires the pH of the suspension to be stabilized by a factor
of about 5.1 to about 5.4 over a similar suspension lacking tobramycin, as
measured over six months of storage at 40°C. Id. Appellant explains that
the claimed stabilization factor is determined by dividing: (a) the percentage
change in pH over 6 months of a composition lacking tobramycin, by (b) the
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Application 12/584, 186
percentage change in pH of a pH-stabilized, tobramycin-containing
composition over 6 months. App. Br. 4, n.1 (citing Examples IV, V, and VI
from Appellant's table on page 10 of the Specification).
As seen from the data regarding Examples IV, V, and VI in
Appellant's table on page 10 of the Specification, a 0.3 weight percent
tobramycin concentration inherently provides the stabilization factor recited
in claim 28. See Spec. 10; FF 8. Indeed, claim 29 limits the tobramycin
concentration to 0.3 weight percent.
Turning to the prior art, as the Examiner points out (Final Action 2-
3), both Guy and Amselem describe ophthalmic loteprednol etabonate
compositions which are suitable for extended periods of storage in the
absence of a buffer, and in which preferred concentrations of the loteprednol
etabonate include 0.5 weight percent, as encompassed by claim 28 and
recited in claim 29 (FF 1, 2). As the Examiner points out (Final Action 2-
3), both Guy and Amselem describe adding tobramycin to compositions that
comprise loteprednol etabonate (FF 4). As the Examiner also points out,
Guy and Amselem do not appear to disclose the concentration of tobramycin
to be included in such compositions.
The PDR, however, discloses that it is useful for ophthalmic
compositions containing a steroid/tobramycin combination to contain 0.3%
tobramycin (FF 5, 6), precisely the concentration recited in claim 29, and, as
discussed above, encompassed by claim 28 's requirement of "a pH
stabilizing amount" of tobramycin. We are therefore not persuaded that the
Examiner erred in finding that the cited references would have prompted an
ordinary artisan to add the claimed amount of tobramycin to
Guy I Amselem' s ophthalmic composition comprising loteprednol etabonate,
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Application 12/584, 186
thereby stabilizing the pH of the composition as required by claims 28 and
29.
It might be true, as Appellant argues (App. Br. 8-9) that the
antimicrobial stability identified by the Examiner and described in
Guy/ Amselem (see Guy, col. 8, 11. 32-58; Amselem, col. 9, 1. 39 through
col. 10, 1. 42), does not demonstrate the pH stability recited in Appellant's
claims 28 and 29. Nonetheless, the facts remain that Guy/Amselem describe
including tobramycin in loteprednol etabonate ophthalmic compositions
intended for extended periods of storage in the absence of a buffer (FF 1, 2,
4), and the PDR discloses that it is useful for ophthalmic compositions
containing a steroid/tobramycin combination to contain 0.3% tobramycin
(FF 5, 6). Thus, the cited prior suggests including, in Guy/Amselem's
ophthalmic compositions, tobramycin at precisely the concentration recited
in claim 29, and, as discussed above, a concentration encompassed by claim
28' s requirement of "a pH stabilizing amount" of tobramycin. We are,
therefore, not persuaded that the prior art cited by the Examiner fails to
suggest all elements of those claims.
Appellant also does not persuade us (App. Br. 8) that In re Shetty
demonstrates error in the Examiner's conclusion of obviousness. We
acknowledge that, despite affirming obviousness of the composition at issue,
our reviewing court's predecessor held that the process of using the
composition to curb appetite had not been shown to be obvious. In re
Shetty, 566 F .2d at 86. Although perhaps not as fleshed out as it might be,
we understand the court in Shetty as concluding that, because the appetite-
suppressing property of the composition at issue was not taught or suggested
in the prior art, and therefore was an unknown, though inherent property, the
11
Appeal2013-006310
Application 12/584, 186
cited prior art did not teach or suggest administering those compositions to
individuals in need of reduced appetite. See id. ("[T]he inherency of an
advantage and its obviousness are entirely different questions. That which
may be inherent is not necessarily known. Obviousness cannot be
predicated on what is unknown.") (citation omitted).
Here, in contrast, as discussed above, both Guy and Amselem
describe combining loteprednol etabonate with tobramycin in ophthalmic
solutions intended for extended storage, and the PDR expressly teaches that
0.3 weight percent of tobramycin is a useful amount of that drug when
combined with a steroid in an ophthalmic solution. Thus, unlike the
situation in Shetty, where there was no suggestion in the prior art for
performing the claimed process, in the instant case the cited prior art
provides a reason for performing the precise process step recited in claim 28.
It might be true that the prior art suggests the claimed step for reasons
other than Appellant's purpose of stabilizing the pH of the composition. As
the Supreme Court has explained, however, "[i]n 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." KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398, 419
(2007).
Appellant contends that the Examiner erroneously pointed to the
Specification's Example 1 in asserting that the evidence advanced to show
unexpectedness was not commensurate in scope with the claimed subject
matter. App. Br. 10. Appellant contends that Examples I, II, IV, and V
possess the pH stability recited in claim 28, and are, therefore,
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commensurate in scope with the claims. Id. at 10-11; see also FF 8
(reproducing Table from page 10 of Spec.).
The compositions of Examples I, II, IV, and V, however, shown by
Appellant as being pH stable, contain the polymers PVP-C30 and PVP-K90
(FF 8), as well as "standard pharmaceutical components" (id.) which are not
specifically identified. As claims 28 and 29 do not recite either the
identified or unidentified additional ingredients present in the compositions
tested by Appellant, Appellant does not persuade us that the Examiner erred
in concluding that those claims are not commensurate in scope with the
evidence of unexpected results asserted by Appellant.
As the Examiner notes, moreover (Ans. 6), to overcome a prima facie
case of obviousness, a showing of unexpected results must be based on a
comparison with the closest prior art. See In re Baxter-Travenol Labs., 952
F.2d 388, 392 (Fed. Cir. 1991).
In the instant case, both Guy and Amselem expressly describe
combining loteprednol etabonate and tobramycin (FF 4). Thus, Appellant's
comparison of the compositions of Examples I, II, IV, and V, that contain
loteprednol etabonate and tobramycin, with compositions that contain only
loteprednol etabonate (FF 8), is not a comparison to the closest prior art,
because Guy and Amselem already taught that tobramycin should be
combined with loteprednol etabonate.
To that end, we note, as Appellant argues (App. Br. 12-13), that
Table 6 of the Specification presents a comparison of different compositions
containing both loteprednol etabonate and tobramycin, with tobramycin
being included at different concentrations in different examples (FF 9).
Regarding the data presented, Appellant contends:
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[T]he pH study indicates that one requires at least 1.0 mg/mL of
tobramycin present in a 5.0 mg/mL loteprednol suspension
(Example 2) to provide the necessary pH stability of the
composition. The data shows that not every composition that
contains 4.3 mg/mL to 5.3 mg/mL of loteprednol and
tobramycin would satisfy claim 28. In other words, not just any
'composition of the prior art' that contains loteprednol and
tobramycin possesses the pH stability of claim 28.
App. Br. 12-13.
As is evident from Table 6, however, pH stability was evaluated only
for nine weeks at 40°C, as opposed to the six months required by claims 28
and 29 (FF 9). Accordingly, we are not persuaded that the data in Table 6 is
commensurate in scope with the stability required of claims 28 and 29, nor
are we persuaded that the data in Table 6 shows the unexpectedness of a
process having the features required by claims 28 and 29.
Appellant contends that the Examiner improperly relies on inherency
to show the obviousness of including tobramycin, in an amount that meets
the stability limitation of claim 28, in a loteprednol etabonate-containing
composition. App. Br. 11-12 (citing In re Rijckaert, 9 F.3d 1531, 1534
(Fed. Cir. 1992) ("That which may be inherent is not necessarily known.
Obviousness cannot be predicated on what is unknown.").
We acknowledge, as our reviewing court has explained, that the
proponent must meet "a high standard in order to rely on inherency to
establish the existence of a claim limitation in the prior art in an obviousness
analysis-the limitation at issue necessarily must be present, or the natural
result of the combination of elements explicitly disclosed by the prior art."
PAR Pharma., Inc. v. TWI Pharms., Inc., 773 F.3d 1186, 1195-96 (Fed. Cir.
2014).
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Thus, the court has held that where the prior art suggests the claimed
subject matter, and the claims merely recite a functional limitation that
results inherently from performing the suggested subject matter, the claimed
subject matter was properly considered obvious. See In re Kao, 639 F.3d
1057, 1070 (Fed. Cir. 2011) ("This is not a case where the Board relied on
an unknown property of prior art for a teaching. Rather, Maloney's express
teachings render the claimed controlled release oxymorphone formulation
obvious, and the claimed 'food effect' adds nothing of patentable
consequence.").
In this case, the Examiner's rejection does not rely on an unknown
inherent property to provide a teaching that suggests performing the claimed
process. Rather, as discussed above, both Guy and Amselem describe
combining loteprednol etabonate with tobramycin in ophthalmic solutions
intended for extended storage, and the PDR expressly teaches that 0.3
weight percent of tobramycin is a useful amount of that drug when
combined with a steroid in an ophthalmic solution. That the pH-stabilizing
effect of including 0.3 weight percent of tobramycin in a loteprednol
etabonate-containing ophthalmic composition might not have been known
does not negate obviousness of performing that step, based on the teaching
in the prior art.
Moreover, as also discussed above, the data regarding Examples IV,
V, and VI in Appellant's table on page 10 of the Specification, shows that a
0.3 weight percent tobramycin concentration inherently provides the
stabilization factor recited in claim 28. See Spec. 10; FF 8. Indeed, claim 29
limits the tobramycin concentration to 0.3 weight percent. Thus, the
pH-stabilizing effect recited in claim 28 is "the 'natural result' of the
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Application 12/584, 186
combination of prior art elements." PAR Pharma., 773 F.3d at 1195
(quoting In re Oelrich, 666 F.2d 578, 581 (CCPA 1981); see also In re Kao,
639 F.3d at 1070 (proper for Board to consult specification to evaluate
inherency).
In sum, for the reasons discussed, Appellant's arguments do not
persuade us that the Examiner failed to make a prima facie case of
obviousness as to claim 28, nor are we persuaded that the Examiner erred in
finding that Appellant's evidence of unexpected results was insufficient to
overcome the prima facie case. Accordingly, we affirm the Examiner's
rejection of that claim as obvious over Guy, Amselem, and the PDR.
As to claim 29, as discussed above, both Guy and Amselem describe
ophthalmic loteprednol etabonate compositions which are suitable for
extended periods of storage in the absence of a buffer, and in which
preferred concentrations of the loteprednol etabonate include 0.5 weight
percent, as recited in claim 29 (FF 1, 2). As discussed above, both Guy and
Amselem describe adding tobramycin to compositions that comprise
loteprednol etabonate (FF 4). As also discussed above, the PDR, however,
discloses that it is useful for ophthalmic compositions containing a
steroid/tobramycin combination to contain 0.3% tobramycin (FF 5, 6),
precisely the concentration recited in claim 29. Accordingly, Appellant's
arguments (App. Br. 13) do not persuade us that an ordinary artisan lacked
motivation to combine the ingredients recited in claim 29 in the
concentrations recited in the claim.
As to Appellant's argument that the cited prior art did not provide a
reasonable expectation of achieving the claimed stability (App. Br. 13), as
discussed above, the pH stabilizing effect recited in claim 28, from which
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claim 29 depends, inherently occurs by adding 0.3 weight percent of
tobramycin to a loteprednol etabonate composition, as suggested by the
references, and therefore, is "the 'natural result' of the combination of prior
art elements." PAR Pharma., 773 F.3d at 1195 (quoting In re Oelrich, 666
F.2d at 581 ).
Accordingly, because Appellant's arguments do not persuade us that
the Examiner erred in maintaining the obviousness rejection of claim 29
over Guy, Amselem, and the PDR, we affirm the rejection as to that claim as
well. Because claim 30 was argued in the same grouping as claim 29 (App.
Br. 5), claim 30 falls with claim 29. 37 C.F.R. § 41.37(c)(l)(iv).
SUMMARY
For the reasons discussed, we affirm the Examiner's rejection of
claims 14, 15, and 25-30 under 35 U.S.C. § 103(a) for obviousness over
Guy, Amselem, and the PDR.
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
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