Harrow IP, LLC

Patent Trials and Appeals Board

Nov 4, 2021

2020005444 (P.T.A.B. Nov. 4, 2021)

UNITED STATES PATENT AND TRADEMARK OFFICE
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
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
15/148,574 05/06/2016 William Wiley 109554-670705-0004-02-08 7327
27148 7590 11/04/2021
POLSINELLI PC
PO Box 140310
KANSAS CITY, MO 64114-0310
EXAMINER
ALAWADI, SARAH
ART UNIT PAPER NUMBER
1619
NOTIFICATION DATE DELIVERY MODE
11/04/2021 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):
patentdocketing@polsinelli.com
rendsley@polsinelli.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte WILLIAM WILEY and DENNIS ELIAS SAADEH

Appeal 2020-005444
Application 15/148,574
Technology Center 1600
____________

Before ULRIKE W. JENKS, JOHN G. NEW, and
RACHEL H. TOWNSEND, Administrative Patent Judges.

JENKS, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to
directed to a pharmaceutical composition. Appellant1 requests review2 of

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42(a). Appellant identifies the real party in interest as Harrow IP,
LLC. Appeal Br. 3.
2 Herein we refer to the Specification filed May 6, 2016 (“Spec.”), Final
Office Action mailed March 8, 2019 (“Final Act.”); Appeal Brief filed
March 4, 2020 (“Appeal Br.”); Examiner’s Answer mailed May 22, 2020
(“Ans.”), and Reply Brief filed July 17, 2020 (“Reply Br.”).
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Application 15/148,574
2
Examiner rejections of the claims as being obvious. We have jurisdiction
under 35 U.S.C. § 6(b).
We AFFIRM.
STATEMENT OF THE CASE
Claims 1–7, and 9–14 are on appeal,3 and can be found in the Claims
Appendix of the Appeal Brief. Claim 1 is representative of the claims on
appeal, and reads as follows:
1. A pharmaceutical composition formulated as a suspension
that consists of:
(a) a dispersed phase consisting of solid particles consisting of a
therapeutically effective quantity of a corticosteroid
independently selected from the group consisting of
prednisone, prednisolone, methylprednisone, corticol,
cortisone, fluorocortisone, deoxycorticosterone acetate,
aldosterone, budesonide, derivatives or analogs thereof, and
pharmaceutically acceptable salts, hydrates and solvates
thereof; and
(b) a dispersion medium consisting of:
(b1) a therapeutically effective quantity of an anti-
bacterial agent independently selected from the group
consisting of quinolone, a fluorinated quinolone and
pharmaceutically acceptable salts, hydrates, solvates,
N-oxides thereof, and combinations thereof;
(b2) a therapeutically effective quantity of a combination
of two pharmaceutically acceptable excipients, the
combination consisting of:
(b2a) a first excipient selected from the group
consisting of non-ionic polyoxyethlene-
polyoxypropylene block copolymers; and

3 We note that the following appeals are related: Appeal No. 2020-005442
(Application Number 15/057,711); Appeal No. 2020-005499 (Application
number 15/061,488); and Appeal No. 2020-005812 (Application Number
14/972,822).
Appeal 2020-005444
Application 15/148,574
3
(b2b) a second excipient selected from the group
consisting of partially cross-linked
polyacrylates, polyoxyethylene sorbitan
monolaurates, polyoxyethylene sorbitan
monopalmitates, polyoxyethylene sorbitan
monostearates, polyoxyethylene sorbitan
monooleates or combinations thereof;
(b3) a therapeutically effective quantity of a glycopeptide
antibiotic selected from the group consisting of
vancomycin, teicoplanin, telavancin, decaplanin,
ramoplanin, gentamicin, tobramycin, amikacin,
cefuroxime, polymyxin B sulfate, and trimethoprim
and combinations thereof;
(b4) a therapeutically effective quantity of a non-steroid
anti-inflammatory drug selected from the group
consisting of bromfenac, ketorolac, etodolac, sulindac,
diclofenac, aceclofenac, nepafenac, tolmetin,
indomethacin, nabumetone, ketoprofen,
dexketoprofen, ibuprofen, flurbiprofen, dexibuprofen,
fenoprofen, loxoprofen, oxaprozin, naproxen, aspirin,
salicylic acid, diflunisal, salsalate, mefenamic acid,
meclofenamic acid, flufenamic acid, tolfenamic acid,
meloxicam, piroxicam, ternoxicam, droxicam,
lornoxicam, isoxicam, celecoxib, rofecoxib,
valdecoxib, parecoxib, lumiracoxib, etoricoxib,
firocoxib, nimesulide, clonixin, licofelone, and
pharmaceutically acceptable salts, hydrates, solvates,
ethers, esters, acetals and ketals thereof and
combinations thereof; and
(b5) a pharmaceutically acceptable carrier selected from
the group consisting of sterile water, hydrochloric
acid, and any combination thereof,
wherein the dispersed phase is dispersed within the
dispersion medium, and wherein at least about 99.8% of all the
solid particles in the dispersed phase have a size of 10 μM or
less,
with the further proviso that the pharmaceutical
composition is an ophthalmic composition that is suitable for
delivery via intraocular injection or via eye drops.
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Appeal Br. 28–29 (Claims Appendix). Claim 10, depends on claim 1
and further recites the concentration of the antibacterial agent,
corticosteroid, and block copolymer.
REJECTIONS
Appellant requests review of the following grounds of rejection made
by Examiner:
I. Claims 1–7, 9, and 11–14 under 35 U.S.C. § 103 as obvious
over Cagle,4 Tsao,5 Domb,6 and Kulshreshtha,7; and
II. Claim 10 under 35 U.S.C. § 103 as obvious over Cagle, Tsao,
Domb, Kulshreshtha, and Babu.8

I. Obviousness over Cagle, Tsao, Domb, and Kulshreshtha
The issue is whether the preponderance of the evidence of record
supports Examiner’s conclusion that the combination of references renders
the claimed composition obvious.
A. Findings of Fact (FF)
FF1. Cagle teaches that ophthalmic surgical procedures that create “a
risk of microbial infections frequently also cause inflammation
of the affected tissues.” Cagle ¶ 5. Thus, it would be convenient
to have compositions “that combine the anti-infective activity
of one or more antibiotics with the anti-inflammatory activity of
one or more steroid or non-steroid agents in a single

4 Cagle et al. US 2002/0193370 A1, published Dec. 19, 2002 (“Cagle”).
5 Tsao et al., US 5,611,464, issued Mar. 18, 1997 (“Tsao”).
6 Domb et al., US 5, 227,165, issued July 13, 1993 (“Domb”).
7 Kulshreshtha et al., US 5,803,966, issued Sept. 8, 1998 (“Kulshreshtha”).
8 Babu et al., US 2007/0049552 A1, published Mar. 1 2007 (“Babu”).
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composition.” Id. In addition to prophylactically treating
patients after surgical procedures, other ophthalmic condition
such as “conjunctivitis, keratitis, blepharitis, dacyrocystitis,
hordeolum and corneal ulcers” can also be treated with the
composition. Id. ¶ 8. The ophthalmic compositions are
“typically administered to the affected ophthalmic . . . tissues
by topically applying one to four drops of a sterile solution or
suspension.” Id. ¶ 38.
FF2. Cagle teaches that “[t]he [antibiotic] compound Moxifloxacin is
most preferred.” Cagle ¶ 27. The composition will contain
moxifloxacin “in a concentration of from about 0.1 to about 1.0
percent by weight (“wt. %”) of the compositions. Id. ¶ 31.
FF3. Cagle teaches that the composition may contain one or more
anti-inflammatory agents. The anti-inflammatory agents “are
broadly classified as steroidal or non-steroidal” agents. Cagle
¶ 32. The composition “will typically contain one or more anti-
inflammatory agents in an amount of from about 0.01 to about
1.0 wt. %.” Id. ¶ 37.
FF4. Cagle teaches that the steroidal anti-inflammatory agents
include “glucocorticoid is selected from the group consisting of
dexamethasone, rimexolone, prednisolone, fluorometholone,
hydrocortisone, mometasone, fluticasone, beclomethasone,
flunisolide, triamcinolone and budesonide.” Cagle, claim 4.
FF5. Cagle teaches that “[t]he preferred non-steroidal anti-
inflammatory agents are: prostaglandin H synthetase inhibitors
(Cox I or Cox II), also referred to as cyclooxygenase type I and
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type II inhibitors, such as diclofenac, flurbiprofen, ketorolac,
. . . naproxen, ibuprofen, bromfenac, ketoprofen,
meclofenamate, piroxicam, sulindac, mefanamic acid,
diflusinal, oxaprozin, tolmetin,” among others. Cagle ¶ 36.
FF6. Cagle teaches that the composition has a pH range between
4.5–8 and osmotic values in the range of 200 to about 400
milliosmoles per kilogram of water, and preferably about
300 mOsm/kg. Cagle ¶ 39.
FF7. Cagle teaches incorporating suitable preservatives into multi-
dose containers at a concentration of 0.001% to 1.0% by
weight. Cagle ¶ 40. “Suitable preservatives include:
polyquatemium-1, benzalkonium chloride, thimerosal,
chlorobutanol, methyl paraben, propyl paraben, phenylethyl
alcohol, edetate disodium, sorbic acid, or other agents known to
those skilled in the art.” Id.
FF8. Cagle teaches that the solubility of the composition may be
enhanced with the inclusion of 0.01% to 2% by weight of a
co-solvent. Cagle ¶ 41. “[C]o-solvents include polysorbate 20,
60, and 80, polyoxyethylene/polyoxypropylene surfactants
(e.g., Pluronic F-68, F-84 and P-103), cyclodextrin, or other
agents known to those skilled in the art.” Id.
FF9. Tsao teaches that “ophthalmic solutions typically include a
preservative or antimicrobial, such as polymyxin B sulfate,
quaternary ammonium compounds, chlorobutanol, organic
mercurials, p-hydroxybenzoic acid esters, certain phenols or
substituted alcohols.” Tsao 1:37–42; 3:48–55 (“Strong cationic
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preservatives include, without limitation thereto, polymyxin B
sulfate, . . . benzalkonium chloride, . . . and mixtures thereof.”).
Tsao teaches that “strong preservative may be selected (1) to
both inhibit microbial growth and kill microorganisms which
inadvertently contaminate the ophthalmic solution upon
exposure to the surroundings or (2) to inhibit the degradation or
deactivation of the active agent.” Id. at 3:35–40.
FF10. Domb teaches “[a] local anesthetic microsuspension system . . .
that includes lipospheres, that are solid, water-insoluble
microparticles that have a layer of a phospholipid embedded on
their surface.” Domb, Abstract. The core contains lidocaine as
an anesthetic. Id. The liposome formulation can be in the form
of suspensions, and also include “antimicrobials agents or
preservatives (such as gentamicin and vancomycin) to reduce
the incidence of local bacterial infections associated with lipid-
based injections.” Id. at 5: 18–21. Domb teaches that the
liposomes can be administered topically. Id. at 5: 26–27. Domb
teaches that other actives may also be included in the
lipospheres such as anti-inflammatories and antimicrobials. See
Id. at 9:4–6.
FF11. Kulshreshtha teaches:
It is generally accepted that particle sizes in ophthalmic
suspensions should be less than 10 μm in order to
minimize irritation. Small drug particle sizes in
pharmaceutical suspensions are desirable for a number of
other reasons as well, including enhanced bioavailability.
Additionally, in comparison with suspensions of particles
of larger sizes, suspensions of particles of about 1 μm or
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less possess superior particulate stability due to the
colloidal nature of the smaller particles.
Kulshreshtha 1: 13–21. Kulshreshtha teaches prednisolone
acetate particles with an average sizes of 1 μm or less. Id. at
3:9–11, 6:64–7:14 (claim 1), 7:15–18 (claim 2 (“wherein the
process produces prednisolone acetate having a number average
particle size of 0.5 μm or less and a particle size distribution
having no particles greater than 5 μm (based on number
distribution).”).
B. Analysis
1. Claim 1
Examiner finds that Cagle teaches ophthalmic compositions
containing prednisolone, a corticosteroid, and moxifloxacin. Final Act. 5;
FF1, FF4. Examiner finds that the composition of Cagle can be administered
as eye drops and that such compositions can contain water. Final Act. 6;
FF1, FF6; Cagle ¶¶ 44–45. Examiner finds that Cagle suggests that the
composition contains “co-solvents can be employed from .01 -2% but does
not teach a combination of polyoxyethylene/polyoxypropylene block with
polyoxyethylene sorbitan monolaurate 20 (polysorbate 20).” Final Act. 6;
FF8. Examiner acknowledges that Cagle does not exemplify a composition
combining different co-solvent but concludes that combining these two or
more co-solvent in order to form a third composition is prima facie obvious.
Final Act. 6. (citing In re Kerkhoven, 626 F.2d 846, 850 (CCPA 1980)).
Because “Cagle teaches that both compounds function as a co-solvent for
adjusting solubility of the composition, then it would have been obvious
[according to Examiner] to incorporate both to arrive at the desired
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solubilizing properties for the composition as both compounds are taught as
excipients (i.e. co-solvents) for ophthalmic use.” Final Act. 7; FF8.
Examiner acknowledges that Cagle does not expressly teach the
presence of a secondary antimicrobial agent such as vancomycin in the
composition. Final Act. 7. Cagle teaches the use of preservatives when
packaging the pharmaceutical product into a multi-dose formulation, and
teaches that such preservatives includes any compound known to those of
ordinary skill in the art. FF7. Examiner looks to Tsao for teaching
antimicrobials such as polymyxin B that can be included as a preservative
for ophthalmic solutions to prevent microbial contamination of a bottle
contents during extended storage. Final Act. 7; FF9. Examiner additionally
cites Domb for teaching that vancomycin also functions as a preservative in
ophthalmic solutions. Final Act. 8; FF10. Based on these combined
teachings, Examiner concludes that
it would have been prima facie obvious to substitute the
preservative of Cagle which function is to provide antimicrobial
protection for vancomycin because the prior art suggests that
antibiotics can also function as preservatives and Domb teaches
that vancomycin has the function of providing antimicrobial
preservative activity and thus suggests its use to prevent
microbial contamination. There would have been a reasonable
expectation of success because Cagle suggests any other known
agent can be supplemented to prevent microbial contamination.
Final Act. 7–8.
Examiner acknowledges that Cagle does not teach a 99.8% population
of particles having particle size of 10 µm or less. Final Act. 8. Cagle teaches
suspensions but is otherwise silent with respect to the size of the particles.
FF1. Kulshreshtha suggests that particles in ophthalmic suspensions should
be less than 10 µm. FF12. Kulshreshtha teaches the production of
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prednisolone acetate particles having an average particle size of less than
10 µm. FF12. In addition, Kulshreshtha teaches that particles that are less
than 1 µm have superior stability. FF12. Based on the combined teachings of
the references, Examiner concludes that it would have been prima facie
obvious to provide the corticosteroid of Cagle in particle form having a
particle size of less than 10 µm and more preferably with particle size of less
than 1 µm. Final Act. 8.
A person of ordinary skill in the art would have been
motivated to do so in order to provide better bioavailability and
superior stability for the steroid particles of Cagle.
There would have been a reasonable expectation of
success as both Cagle and Kulshreshtha et al. disclose
ophthalmic formulations which contain corticosteroids.
Final Act. 8.
Upon consideration of the evidence on this record, and each of
Appellant’s contentions, we find that the preponderance of evidence
supports Examiner’s conclusion that the subject matter of Appellant’s claims
is unpatentable. Accordingly, we affirm Examiner’s rejections for the
reasons set forth in the Answer and Final Office Action, which we adopt as
our own, including Examiner’s responses to Appellant’s arguments. We
address Appellant’s contentions below.
(a) Cagle contains preservatives
Appellant contends that “one of skill in the art in view of Cagle would
understand that an anti-inflammatory ophthalmic composition without a
preservative would not be suitable for such a use due to the high potential
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for microbial contamination.” Appeal Br. 19. Appellant relies on the Saadeh9
Declaration to establish that in order to use the composition of Cagle one of
ordinary skill in the art would understand that the composition requires a
preservative at a level of from 0.001% to 1.0% by weight.” Id. at 20 (citing
Saadeh Declaration 2–3).
We agree with Examiner that the Saadeh Declaration, considered in
light of the evidence of obviousness, does not establish non-obviousness
because the claims do not exclude preservatives. Ans. 5. We understand that
the claims utilize the transitional phrase “consists of” which closes the claim
to exclude elements not specified in the claim. “[C]losed transition phrases
such as ‘consisting of’ are understood to exclude any elements, steps, or
ingredients not specified in the claim.” AFG Indus., Inc. v. Cardinal IG Co.,
239 F.3d 1239, 1245 (Fed. Cir. 2001). As Examiner explains the “claims do
not exclude preservatives from being present because claim 1 can include
vancomycin or polymyxin B sulfate antimicrobial.” Ans. 4.
In order to arrive at the conclusion that the claims are obvious,
Examiner acknowledges that Cagle does not teach using a glycopeptide
antibiotic such as vancomycin or polymyxin B sulfate antimicrobial,
Examiner however concluded that it would have been obvious to substitute
these antimicrobials which are taught in the prior art to also function as
preservatives. Ans. 4 (“The preservatives of which include polymyxin B
sulfate function to provide antimicrobial activity, . . . [and] that antimicrobial
agents such as vancomycin also function as a preservative as it reduces
bacteria.”). Therefore, after the obvious substitution of vancomycin or

9 Declaration under 37 C.F.R. §1.132 by Dr. Dennis Saadeh submitted
July 19, 2018 (“Saadeh Declaration”).
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polymyxin B sulfate for the preservative recited in Cagle, the composition
meets the claimed limitations. In other words, when the preservative is
vancomycin or polymyxin B sulfate the composition meets the claimed
glycopeptide antibiotic element as recited in the claim.
Examiner explains that these glycopeptide antibiotics can have dual
function as a preservative or antibiotic.
Given the function of a preservative is to provide antimicrobial
activity to the composition, and the instant claims include
vancomycin or polymyxin B sulfate as an antimicrobial agent,
the Examiner maintains that the claims do not necessarily
exclude preservatives from maintaining antimicrobial stability
of the ophthalmic composition. The instantly claimed
composition provides vancomycin which reduces or inhibits
bacteria and thus Appellant’s ophthalmic product also contains
a preservative agent present in the composition.
Ans. 5; see also FF9 (“Strong cationic preservatives include, without
limitation thereto, polymyxin B sulfate”); FF10 (“The liposome formulation
can be in the form of suspensions, and also include ‘antimicrobials or
preservatives (such as gentamicin and vancomycin) to reduce the incidence
of local bacterial infections associated with lipid-based injections.’”).
Cagle may allow for the inclusion of a combination of preservatives
but there is no teaching in Cagle that multiple preservatives are required. See
FF7. Cagle teaches that the preservative when present is in a range from
0.001% to 1.0%, and preservatives are usually added when the formulation
is packaged into a multi-dose format. FF7. Appellant has not established that
at a concentration of 1.0% in the composition vancomycin or polymyxin B
sulfate would not provide a therapeutically effective quantity of the
glycopeptide antibiotic as recited in the claim. Accordingly, we are not
persuaded by Appellant’s contention that the combination as articulated by
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Examiner does not meet all the claim elements and contains impermissible
additional ingredients.
(b) Long felt need
Appellant contends that there was long felt and unmet need for
combination therapy. Appellant relies on the Wiley10 Declaration for this
position. Appeal Br. 20. Appellant contends that “by combining these
medications into a single composition, the claimed invention goes against
conventional wisdom by eliminating the need for a waiting period between
administering each medication.” Id. (citing Wiley Declaration 2–3).
We are not persuaded. Establishing long-felt need requires objective
evidence that an art-recognized problem existed for a long period of time
without solution. In particular, the evidence must show that the need was a
persistent one that was recognized by those of ordinary skill in the art. See In
re Gershon, 372 F.2d 535, 538 (CCPA 1967). The relevance of long-felt
need and the failure of others to the issue of obviousness depends on several
factors. First, the need must have been a persistent one that was recognized
by those of ordinary skill in the art. See Orthopedic Equip. Co. v. All
Orthopedic Appliances, Inc., 707 F.2d 1376, 1382 (Fed. Cir. 1983); see also
In re Gershon, 372 F.2d 535, 538 (CCPA 1967). Second, the long-felt need
must not have been satisfied by another before the invention by applicant.
See Newell Co. v. Kenney Mfg. Co., 864 F.2d 757, 768 (Fed. Cir. 1988)
(“[O]nce another supplied the key element, there was no long-felt need or,
indeed, a problem to be solved . . . .”) Third, the invention must in fact

10 Declaration under 37 C.F.R. § 1.132 by Dr. William Wiley submitted
July 19, 2018 (“Wiley Declaration”).
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satisfy the long-felt need. See In re Cavanagh, 436 F.2d 491, 496 (CCPA
1971) (One must also show that the others who failed had knowledge of the
critical prior art.). “[L]ong-felt need is analyzed as of the date of an
articulated identified problem and evidence of efforts to solve that problem.”
Texas Instruments, Inc. v. ITC, 988 F.2d 1165, 1178 (Fed. Cir. 1993).
We agree with Examiner that Appellant’s Wiley Declaration of long
felt need is unpersuasive because Cagle already suggests pharmaceutical
compositions that encompass combination therapies by reciting that the
composition can contain “one or more anti-inflammatory agents” in
conjunction with the other elements as recited in the claim. Ans. 6; FF3. In
other words, Cagle provides the instructions for solving the problem of
administering antibiotics and anti-inflammatory agents at the same time. See
FF1–FF8.
Cagle at paragraph [0038] expressly teaches that the
composition is administered to the affected ophthalmic tissue
by applying one to four drops of the suspension composition
one to four times daily and can be packaged in a multidose
format therefore eliminates the need for multiple single use
vials, see paragraphs [0038]-[040] and claims 1-10.
Ans. 6; FF1. The fact that single formulation combination therapy is not
presently used and is not the standard of care in treating patients is not
evidence that these formulations are not obvious. See Purdue Pharma L.P. v.
Endo Pharmaceuticals Inc., 438 F.3d 1123, 1134 (Fed. Cir. 2006) (“[T]he
quantum of proof necessary for FDA approval is significantly higher than
that required by the PTO.”). Here, Cagle suggests producing a single
composition for providing combination therapy that combines anti-infective
activity of an antibiotic with one or more anti-inflammatory agents. FF1,
FF3. Thus, Cagle supplies the key element of including multiple actives in
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one composition. Accordingly, we are not persuaded that evidence of record
sufficiently supports Appellant’s long felt need argument in order overcome
Examiner’s prima facie case of obviousness.
(a) Lacks motivation
Appellant contends that Cagle is absolutely silent with regard to
combining polyoxyethylene/polyoxypropylene with polysorbate. Appeal Br.
22. In addition, Appellant contends that “[a]s one skilled in the art of
colloidal chemistry would understand, the addition of the second excipient
does not enhance solubility of the composition.” Id. Appellant contends that
in order to improve solubility of the composition one would have been
motivated to add a second agent that has an HLB value that is higher than
the first excipient. Id. at 21 (citing Exhibits 1–6). Appellant argues that one
of ordinary skill could not find a second solubilizing agent that is greater
HLB than polyoxyethylene/ polyoxypropylene block copolymers. Id.
We are not persuaded. Appellant’s argument that one could not find a
second solubilizing agent that has an HLB that is greater than
polyoxyethylene/polyoxypropylene block copolymers constitutes no more
than a conclusory argument without supporting evidence, and is
unpersuasive. “Attorney’s argument in a brief cannot take the place of
evidence.” In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974). Appellant’s
argument focuses on one co-solvent, polyoxyethylene/polyoxypropylene
block copolymer, listed in Cagle. FF8. Cagle does not indicate that
polyoxyethylene/polyoxypropylene block copolymers is the preferred co-
solvent or is otherwise reasonably selected as the starting point for co-
solvents used in the composition. Indeed, none of the examples provided in
Cagle use a co-solvent indicating that the inclusion of a co-solvent is
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optional. Thus, Appellant’s hypothetical starting point of using
polyoxyethylene/polyoxypropylene block copolymer as the first co-solvent
is not persuasive. Furthermore, as Examiner explains that “if adding
polysorbate to the polyoxyethylene/polyoxypropylene would lower the HLB
and decrease the solubility enhancement, the opposite is also true where
when polyoxyethylene/polyoxypropylene is added to the polysorbate to
enhance the solubility given its higher HLB value.” Ans. 10.
We agree with Examiner that Appellant has not established any
criticality for the addition of a second co-solvent and agree “that selection of
known excipients for their established function of providing the desired
solubility would have been well within the purview of an ordinary skilled
artisan in the pharmaceutical arts.” Ans. 11. Accordingly, Appellants
arguments do not persuade us that Examiner erred in concluding that the
claims are obvious.
(b) Antimicrobial and preservative agents
Appellant contends that the “antimicrobials and preservatives of
Domb are not interchangeable” because “Domb provides a list of
biologically active materials, which includes antimicrobials but excludes
preservatives, that may be encapsulated in the lipospheres.” Appeal Br. 22.
Appellant contends that “one of skill in the art in view of Tsao would
understand that a substance intended to prevent contamination of a solution
is not the equivalent of a substance that prevents bacterial infection to a
subject being administered the solution.” Reply Br. 2.
We are not persuaded by Appellant’s contention that antibiotics and
preservatives are not interchangeable. According to the Specification, “[t]he
terms ‘anti-bacterial’ and ‘antibiotic’ are broadly covered by the term
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‘antimicrobial’ and are used herein interchangeably, refer to substances or
compounds that destroy bacteria and/or viruses and/or inhibit the growth
thereof via any mechanism or route.” Spec. ¶ 23. Thus, the Specification
provides that a compound that inhibits the growth of bacteria regardless of
application is reasonably considered “an antibiotic.” The Specification
provides that “[t]he term ‘therapeutically effective amount’ is defined as the
amount of the compound or pharmaceutical composition that will elicit the
biological or medical response of a tissue, system, animal or human that is
being sought by the researcher, medical doctor or other clinician.”
Spec. ¶ 37. In this definition, there is also no requirement that an antibiotic
safeguards a patient from microbial infection, all that is required is that there
is a “biological or medical response of a tissue.”
Thus, a compound that would prevent the growth of bacteria would at
the same time also prevent degradation by bacteria because the bacteria are
not active as they are not growing. Domb teaches that “[t]he liposome
formulation can be in the form of suspensions, and also include
‘antimicrobials or preservatives (such as gentamicin and vancomycin) to
reduce the incidence of local bacterial infections associated with lipid-based
injections.’” FF10. Thus, Domb identifies gentamicin and vancomycin as
having dual function as an antimicrobial and a preservative. Tsao teaches
that “[s]trong cationic preservatives include, without limitation thereto,
polymyxin B sulfate.” FF9. The dual function of the same glycopeptide
antibiotic compound having both antibiotic and preservative is supported.
Compare FF9 (identifying polymyxin B sulfate as a preservative) with Spec.
¶ 44 (identifying polymyxin B sulfate as an antibiotic). Accordingly, we
agree with Examiner, given that “the function of a preservative is to provide
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antimicrobial activity to the composition, and the instant claims include
vancomycin[, polymyxin B sulfate, or calcium EDTA], . . . the claims do not
necessarily exclude preservatives from maintaining antimicrobial stability of
the ophthalmic composition.” Ans. 12.
Examiner explains that Cagle teaches that
[t]he use of polyquaternium-1 as the antimicrobial preservative
is preferred.” Here, preservatives and antimicrobial agents are
not distinguished. Per Domb, preservatives or antimicrobials
such as vancomycin are used to reduce bacteria. Thus
preservative and antimicrobial are interchangeable as suggested
by both Cagle and Domb. Examiner further submits that even
Tsao recognizes that antimicrobial agents (i.e. polymyxin B
sulfate) are a preservative and are used interchangeably as a
preservative or antimicrobial.
Ans. 12; FF10 (“The liposome formulation can be in the form of
suspensions, and also include ‘antimicrobials or preservatives (such as
gentamicin and vancomycin) to reduce the incidence of local bacterial
infections associated with lipid-based injections.’”). We find that the
evidence of record supports Examiner’s conclusion that the same compound
can have dual function as a preservative or antimicrobial. See FF10–FF11.
Hence, we find Examiner’s reason for substituting vancomycin or
polymyxin B sulfate for the preservative in Cagle is supported in the record.
2. Claims 2–7, 9, and 11–14
With respect to these rejections, Appellant relies on the same
arguments relied upon with respect to claim 1, discussed above. See Appeal
Br. 23–26. Thus, for the reasons discussed above, we find that Examiner has
established a prima facie showing of obviousness with respect to claim 1.
Accordingly, we affirm the rejection of claims 2–7, 9, and 11–14 as well.
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C. Conclusion
We conclude that the preponderance of the evidence of record
supports Examiner’s conclusion that the combination of Cagle, Tsao, Domb,
and Kulshreshtha renders the composition of claims 1–7, 9, and 11–14
obvious. We thus affirm the rejection of claims 1–7, 9, and 11–14 under
35 U.S.C. § 103(a) as being obvious.
II. Obviousness over Cagle, Tsao, Domb, Kulshreshtha, and Babu
The issue is whether the preponderance of the evidence of record
supports Examiner’s conclusion that the combination of references renders
the claimed composition obvious.
A. Findings of Fact (FF)
FF12. Babu teaches pharmaceutical compositions comprising a
fluoroquinolone active agent. Babu teaches a pharmaceutical
composition comprising:
a) 1 to 100 mg/mL of a fluoroquinolone active agent such
as for example gatifloxacin and moxifloxacin. Babu,
claims 1 and 9.
b) 0 to 100 mg/mL of a steroidal anti-inflammatory agent
such as for example cortisone, hydrocortisone,
corticosterone, deoxycorticosterone, prednisolone,
methylprednisolone, meprednisone, triamcinolone,
paramethasone, fluprednisolone, betamethasone,
dexamethazone, fludrocortisone, and combinations
thereof; or non-steroidal anti-inflammatory agent such as
for example of aspirin, diclofenac, indomethacin,
sulindac, ketoprofen, flurbiprofen, ibuprofen, naproxen
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and combinations thereof. Babu, claims 1, 10, and 11.
c) 1 to 50% by weight of a cyclodextrin. Babu, claim 1, see
also ¶ 7 (“Sulfoalkyl ether cyclodextrin derivatives and
their use as solubilizing agents for water insoluble drugs
for pharmaceutical administration.”)
d) 0 to 25 molar equivalents of a hydroxy acid. Babu,
claim 1, see also ¶ 47 (“Any suitable hydroxy acid may
be used to carry out the present invention, including but
not limited to citric acid, ascorbic acid, malic acid, and
tartaric acid, gluconic acid, lactic acid, treonic acid, and
α, , γ, δ or higher order aliphatic, alicyclic or aromatic
hydroxy acids.”).
e) 0 to 20% by weight of a co-solubilizer. Babu claim 1, see
also ¶ 15 (“co-solubilizer such as a vitamin E derivative,
detergents such as Tweens or pluronics, etc.”), ¶ 50
(“Such co-solubilizers include, but are not limited to,
Pluronics (F-68, F-84 and P-103), Polaxamers, Vitamin E
TPGS, Tweens (20, 60, 80), aliphatic alcohols and other
agents known to those skilled in the art.”).
The pharmaceutical composition also contains water to balance and has a pH
between 4 and 7. Babu claim 1.
B. Analysis
With respect to claim 10, Examiner acknowledges that Cagle, Tsao,
Domb, and Kulshreshtha do not recite the concentrations of the components
and, therefore, Examiner relies on Babu for teaching these limitations. See
Final Act. 9–10; FF12. Appellant contends “that because Babu is relied upon
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for disclosing compositions of components having the claimed concentration
ranges, Babu fails to cure the above-discussed deficiencies of Cagle
modified by Tsao, Domb, and Kulshreshtha.” Appeal Br. 26; Reply Br. 4.
We conclude, considering the totality of the cited evidence and
arguments, that the preponderance of the evidence supports Examiner’s
conclusion of obviousness with respect to claim 1 (see above I.B), and
determine that Appellant has not provided sufficient rebuttal evidence or
evidence of secondary considerations that outweighs the evidence
supporting Examiner’s conclusion. Thus, the rejection of claim 10 is
affirmed for the same reasons discussed above with respect to claim 1 (see
above I.B).

DECISION SUMMARY
In summary:
Claim(s)
Rejected
35 U.S.C.
§
Reference(s)/Basis  Affirmed Reversed
1–7, 9,
11–14
103 Cagle, Tsao, Domb,
Kulshreshtha 
1–7, 9,
11–14

10 103 Cagle, Tsao, Domb,
Kulshreshtha, Babu
10
Overall
Outcome
1–7, 9–14

TIME PERIOD FOR RESPONSE
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