Harrow IP, LLC

Patent Trials and Appeals Board

Nov 4, 2021

2020005442 (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.
15/057,711 03/01/2016 William Wiley 109554-670703-0004-02-05 5165
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

Appeal 2020-005442
Application 15/057,711
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 directed
to a pharmaceutical composition. Appellant1 requests review2 of Examiner’s

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 March 1, 2016 (“Spec.”), Final
Office Action mailed May 23, 2019 (“Final Act.”); Appeal Brief filed
February 24, 2020 (“Appeal Br.”); Answer mailed May 22, 2020 (“Ans.”),
and Reply Brief filed July 17, 2020 (“Reply Br.”).
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rejections of the claims as being indefinite and obvious. We have
jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
STATEMENT OF THE CASE
Claims 1, 2, 6–12, and 35–41 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, wherein the corticosteroid is present at a
concentration of between about 0.1 mg/mL and 100 mg/mL;
and
(b) a dispersion medium consisting of:
(b1) a therapeutically effective quantity of an anti-bacterial
agent independently selected from the group
consisting of moxifloxacin, gatifloxacin, and
pharmaceutically acceptable salts, hydrates, solvates,
N-oxides thereof, and combinations thereof;
(b2) a therapeutically effective quantity of a
pharmaceutically acceptable solubilizing and
suspending agent selected from the group consisting
of non-ionic polyoxyethlene-polyoxypropylene block
copolymers, polysorbates, and combinations thereof;

3 Appellant identifies Appeal No. 2020-005444 (Application Number
15/148,547) as related. Appeal Br. 4. We note that the following appeals are
also related: Appeal No. 2020-005499 (Application Number 15/061,488)
and Appeal No. 2020-005812 (Application Number 14/972,822).
Appeal 2020-005442
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(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, 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, wherein the non-steroid anti-
inflammatory drug is present at a concentration of
between about 0.1 mg/mL and 100 mg/mL; and
(b5) a pharmaceutically acceptable carrier selected from
the group consisting of edetate calcium disodium,
hydrochloric acid, sterile water and any combination
thereof,
wherein the pharmaceutical composition has a pH of about
6.0-6.5 or about 7.4-7.8, wherein the dispersed phase is
dispersed within the dispersion medium, wherein at least about
99.8% of all the solid particles in the dispersed phase have a
size of 10 μ[m] or less, and wherein the pharmaceutical
composition loses no potency and maintains stability after
about six months of storage.
Appeal Br. 36–37 (Claims Appendix).
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Claim 35, the only other independent claim, does not contain
the glycopeptide antibiotic element (b3) of claim 1 but contains all the
other limitations of claim 1.
REJECTIONS
Appellant requests review of the following grounds of rejection made
by Examiner:
I. Claims 1, 2, 6–12, and 35–41 under 35 U.S.C. §112(b) as being
indefinite;
II. Claims 1, 2, and 6–12 under 35 U.S.C. §103 as obvious over
Cagle4 in view of Heier,5 Tsao,6 Domb,7 Kassem,8 and
Babu;9and
III. Claims 35–41 under 35 U.S.C. §103 as obvious over Cagle in
view of Heier, Scott,10 Kassem, and Babu.
I. Indefiniteness
Examiner finds that the limitation “loses no potency and maintains
stability after about six months” as recited in independent claims 1 and 35 is
unclear. Final Act. 26. Specifically, Examiner finds that it is not clear
whether the composition maintains stability for the first 6 months or whether

4 Cagle et al. US 2002/0193370 A1, published Dec. 19, 2002 (“Cagle”).
5 Heier et al., Ketorolac versus Prednisolone versus Combination Therapy in
the Treatment of Acute Pseudophakic Cystoid Macular Edema, 107
OPHTHALMOLOGY 2034–39 (2000) (“Heier”).
6 Tsao et al., US 5,611,464, issued Mar. 18, 1997 (“Tsao”).
7 Domb et al., US 5,227,165, issued July 13, 1993 (“Domb”).
8 Kassem et al., Nanosuspension as an ophthalmic delivery system for
certain glucocorticoid drugs, 340 INT’L J. PHARMACEUTICS 126-133 (2007)
(“Kassem”).
9 Babu et al., US 2007/0049552 A1, published Mar. 1 2007 (“Babu”).
10 Scott, US 2009/0092574 A1, published Apr. 9, 2009.
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it maintains stability from 6 months onward. Final Act. 26. Additionally,
Examiner finds that “maintains stability” is a term of degree that has not
been defined in the Specification and therefore one of ordinary skill in the
art would not know the meets and bound of this limitation. Final Act. 26–27.
Appellant contends that they tested their formulation for stability by
looking at particle size distribution after 6 months of storage. Appeal Br. 33–
34; (citing Spec. ¶¶ 77–78). According to the Specification, the formulation
“was also tested for stability after 6 months of storage. After this period of
storage, no loss of potency was observed (as measured by HPLC); the
formulation was visually stable at room temperature and readily re-
suspended with gentle shaking with no increase of particle size or
flocculation.” Spec. ¶ 78. Based on this disclosure, Appellant contends that
“stable” and “maintains stability” is reasonably understood by one of
ordinary skill in the art to “refer[] to a suspension that is free from
unacceptable coagulation, clumping and flocculation of solid particles.”
Appeal Br. 34. “[B]ecause the formulations were tested ‘after 6 months of
storage,’ one of skill in the art would understand that the composition loses
no potency within the first six months.” Id.
We find that Appellant has the better position. The limitation “loses
no potency and maintains stability after about six months” as recited in the
independent claims is reasonably understood in light of the Specification to
mean that the composition does not lose potency for a least 6 months, and it
is understood that the composition is free of coagulation, clumping, and
flocculation of solid particles which is known to contribute to loss of
potency. See Spec. ¶¶ 49, 78. There is no requirement that Appellant has to
test the composition beyond 6 months. Therefore, we determine that the
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evidence of record does not support Examiner’s conclusion that the claims
are indefinite.
II. Obviousness over Cagle, Heier, Tsao, Domb, Kassem, 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)
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
composition.” Id. ¶ 5. 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 composition.” Id. ¶ 31.
FF3. Cagle teaches that the composition may contain one or more
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anti-inflammatory agents. The anti-inflammatory agents “are
broadly classified as steroidal and 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
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
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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. Heier teaches administering “ketorolac tromethamine 0.5%
ophthalmic solution, prednisolone acetate 1.0% ophthalmic
solution, and ketorolac and prednisolone combination therapy
in the treatment of acute, visually significant, cystoid macular
edema (CME) occurring after cataract extraction surgery.”
Heier, Abstract. Heier concludes that combination therapy
offers benefits over monotherapy (Heier, Abstract), and
“recommend that combination therapy of a topical steroid and
NSAID be considered for the treatment of acute CME.” Heier
2038.
FF10. 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 1:39–42; 3:48–55 (“Strong cationic
preservatives include, without limitation thereto, polymyxin B
sulfate, . . . benzalkonium chloride, . . . and mixtures thereof.”).
Tsao also identified poly(quatemary ammonium) compounds as
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suitable preservatives. Id. at 3:55. Tsao teaches that “strong
preservatives may be selected (1) to both inhibits microbial
growth and kill microorganism which inadvertently contaminate
ophthalmic solution upon exposure to the surroundings or (2) to
inhibit the degradation or deactivation of the active agent.” Id. at
3:35–39.
FF11. 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 “antimicrobial 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.
FF12. Kassem teaches the use of nanosuspensions for ophthalmic
drug delivery “of three practically insoluble glucocorticoid
drugs; hydrocortisone, prednisolone and dexamethasone.”
Kassem, Abstract. “Nanosuspensions are sub-micron colloidal
dispersions of pure drug particles in an outer liquid phase.” Id.
at 126. Kassem teaches the production of 0.1% drug
suspensions of prednisolone having a mean particle size of
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211 nm, 1.626 µm, and 4.0 µm. Table 2 of Kassem, reproduced
below, shows the particle size distribution.

The table above shows the particle size distribution for particles
that are sorted into a mean particle size of 211 nm, 1.626 µm,
and 4.0 µm. Id. at 128. Kaseem teaches that compared to
solution and micro-crystalline suspensions, nanosuspensions
“exhibit a higher intensity of drug action (expressed as IOPmax)
and higher extent of drug absorption (expressed as AUC).” Id.
at 132. Kassem concludes that “[n]anosuspensions are effective
in ophthalmic drug delivery allowing lower doses and less
frequent instillation. . . . Nanosuspensions, besides being more
convenient to the patient, would provide an alternative therapy
with fewer side effects.” Id.
FF13. Babu teaches pharmaceutical compositions comprising a
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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 moxifloxcin. 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
and combinations thereof. Babu, claims 1, 10, and 11.
c) 1 to 50% by weight of a cyclodextrin. Babu, claim 1, see
also id. ¶ 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 id. ¶ 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.”).
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e) 0 to 20% by weight of a co-solubilizer. Babu claim 1, see
also id. ¶ 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.”).
f) The pharmaceutical composition also contains water to
balance and has a pH between 4 and 7. Babu claim 1.
B. Analysis
1. Claim 1
Examiner finds that Cagle teaches ophthalmic compositions
containing prednisolone a corticosteroid and moxifloxacin. Final Act. 6;
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 does not expressly
teach a combination of prednisolone with ketorolac or bromfenac (non-
steroidal anti-inflammatory), however Cagle teaches that one or more anti-
inflammatory agents are combinable in the formulation and that both are
recognized as anti-inflammatory agents.” Final Act. 6; FF3–FF5.
Examiner acknowledges that Cagle does not exemplify a composition
combining both a steroidal anti-inflammatory and a non-steroidal anti-
inflammatory but concludes that combining these two classes of active
agents 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)). Examiner
relies on Heier to provide additional support to establish that combination
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therapy would have beenobvious based on the teachings of Cagle.
Specifically, Examiner finds “Heier teaches that combination therapy of a
steroid and non-steroidal anti-inflammatory offers benefits over
monotherapies using either alone.” Final Act. 7; FF9. In other words, Heier
provides motivation for combining the two different classes of anti-
inflammatory agents into a single composition.
Examiner acknowledges that Cagle “does not expressly teach the
presence of a secondary antimicrobial agent such as vancomycin in the
composition.” Final Act. 7. Examiner, however, finds that Cagle teaches the
use of preservatives when packaging the pharmaceutical product into a
multi-dose formulation, and that Cagle teaches that such preservatives
“includes any compound known to those of ordinary skill in the art.” Final
Act. 7; FF7. Examiner looks to Tsao for teaching antimicrobials such as
polymyxin B that can be included as a preservative for ophthalmic solutions.
Final Act. 7; FF10. Examiner additionally cites Domb for teaching that
vancomycin also functions as a preservative in ophthalmic solutions. Final
Act. 8; FF11. Based on these combined teachings, Examiner concludes that
it would have been prima facie obvious to substitute the
preservative of Cagle whose 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 activity and thus suggests its use is to prevent
microbial contamination.
Final Act. 8.
Examiner acknowledges that Cagle does not teach a particle size for
the steroid suspension and looks to Kasseem for disclosing “prednisolone
nanosuspensions [that] enhance the rate, drug absorption and increase
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duration of drug action and yield improved ophthalmic bioavailability of the
drug.” Final Act. 8; see also FF1 (“The ophthalmic compositions are
‘typically administered to the affected ophthalmic . . . tissues by topically
applying one to four drops of a sterile solution or suspension.’” (emphasis
added)). 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. 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 enhanced
drug absorption for the corticosteroid particles of Cagle. One
would have been further motivated to provide the particles at
less than 10 microns as Kasseem also suggests that this allows
for administration of lower doses due to the increased
bioavailability of providing nanoparticulate size ranges.
Final Act. 8–9.
Examiner acknowledges that Cagle does not teach the particular
concentrations of moxifloxacin, prednisolone, polyoxyethylene/
polyoxypropylene block copolymers, corticosteroid, and the non-steroid
anti-inflammatory drug. Final Act. 9. Examiner finds that Babu teaches an
ophthalmic composition containing the recited ingredients and also provides
a suitable range for each of these listed ingredients of the claimed
composition. Final Act. 9; FF13. Based on the combined teachings,
Examiner concludes that the “general conditions” for formulating an
ophthalmic composition containing “fluoroquinolones including
moxifloxacin, anti-inflammatory agents and poloxamers can be combined in
overlapping ranges and suggests that the composition is used for topical
treatment of bacterial infections” such that varying the various components
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requires no more than routine experimentation. Final Act. 10 (citing MPEP
2144.05).
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) Combining steroidal and non-steroidal anti-
inflammatory agents
Appellant contends that “[a]t no time does Cagle teach, suggest, or
claim a composition that includes both steroidal and non-steroidal anti-
inflammatory agents.” Appeal Br. 22. Appellant relies on the Saadeh11
Declaration to establish the importance of selecting a component from a
steroidal anti-inflammatory agent and a component from a non-steroidal
anti-inflammatory agent, because having two active agents that fall into the
same class “would not provide the analgesic properties of the claimed
invention.” Appeal Br. 23. Additionally, Appellant contends “that Babu is
[also] silent with regard to combining a steroid and a non-steroidal anti-
inflammatory agent.” Appeal Br. 26.
Examiner finds that Cagle teaches both steroidal and nonsteroidal
anti-inflammatory agents, acknowledging, however, that Cagle does not
exemplify a composition including both classes of ingredients. We agree

11 Declaration under 37 C.F.R. §1.132 by Dr. Dennis Saadeh submitted
July 19, 2018 (“Saadeh Declaration”).
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with Examiner that it would have been obvious at the time the invention was
made to combine two compositions each taught in the art to be useful for the
same purpose in order to arrive at the third composition used for the same
purpose. Ans. 5 (citing Kerkhoven, 626 F2d 846, 850). In addition, we agree
with Examiner that Heier’s teaching “that [the] combination of steroids with
NSAIDS (non-steroids anti-inflammatory) provides improvement in the eye
than use of either alone” provides motivation to make the combination.
Ans. 5, see also Ans. 7 (“Heier teaches that combination therapy of a steroid
and NSAID offers benefits over monotherapies using either alone, with
patients experiencing better visual recovery, thus the prior art already
suggests that a combination of the steroid with non-steroidal anti-
inflammatories is better than selecting one over the other, see abstract and
results.”); FF9.
We agree with Examiner that it is not necessary for the prior art to
teach the combination to achieve the same advantage as disclosed by
Appellant’s Specification. Ans. 6. MPEP 2144 (IV) states “the reason or
motivation to modify the reference may often suggest what the inventor has
done, but for a different purpose or to solve a different problem. It is not
necessary that the prior art suggest the combination to achieve the same
advantage or result discovered by Applicant. See, e.g., In re Kahn, 411 F.3d
977, 987 [] (Fed. Cir. 2006).”
We agree with Examiner that Saadeh Declaration when considered
together with the evidence of obviousness is insufficient to establish the
claimed invention is non-obvious. Cagle’s teaching that one or more anti-
inflammatory agents can be included in the composition suggests three
possible combinations: the inclusion of two or more steroidal anti-
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inflammatory agents, the inclusion of two or more non-steroidal anti-
inflammatory agents, or the inclusion of at least one steroidal anti-
inflammatory agent in conjunction with at least one non-steroidal anti-
inflammatory agent. FF3. Because the genus is small and each combination
readily envisioned by one of ordinary skill in the art, we agree with
Examiner that a composition based on the selection of one anti-
inflammatory from each class would have been obvious.
We are also not persuaded that “one of skill in the art viewing Cagle
would not realize the importance of including one of each type of agent to
arrive at the claimed invention.” Saadeh Declaration 3. As already explained
above, the genus of possible combinations when considering one or more
anti-inflammatory agents is small. Here, the Saadeh Declaration does not
provide any evidence that would suggest that some combinations of steroidal
anti-inflammatory in conjunction with a non-steroidal anti-inflammatory do
not produce the desired effect. Accordingly, we are not persuaded by
Appellant’s contention that a combination is not obvious based on the cited
art.
(b) Long felt need
Appellant contends that there was long felt and unmet need for
combination therapy. Appellant relies on the Wiley12 Declaration to support
this position. Appeal Br. 23. 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

12 Declaration under 37 C.F.R. § 1.132 by Dr. William Wiley submitted
July 19, 2018 (“Wiley Declaration”).
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administering each medication.” Id. at 24 (citing Wiley Declaration 2–3).
Appellant further relies on the Tyson13 Declaration to establish “that there is
[an] art recognized problem that has existed for a long period of time
without solution, as evidenced by the fact that cataract patients are still
provided with a multitude of disposable vials of the medications and must
instill the correct ones at the correct times.” Id.
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
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

13 Declaration under 37 C.F.R. §1.132 by Dr. Sydney L. Tyson, MD, MPH,
submitted February 6, 2019 (“Tyson Declaration”).
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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 encompasses 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. 8; 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.
We are also not persuaded by Appellant’s contention that “[t]he
claimed composition meets a long-felt yet unfulfilled need and goes against
accepted wisdom in the art.” Tyson Declaration 2; Wiley Declaration 4 (“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.”). A suggestion that
in practice patients still needed to utilize multiple solutions supplied in
separate vials for administering the individual drops over an extended period
of time does not provide evidence that an art-recognized problem existed for
a long period of time without solution. Tyson Declaration 4. The fact that
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
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provides anti-infective activity of an antibiotic, such as moxifloxacin, in
conjunction with anti-inflammatory agents. FF1, FF3. Thus, Cagle supplies
the key element of including multiple actives in one composition.
Accordingly, Appellants contentions do not persuade us that Examiner erred.
(c) Antimicrobial and preservative agents
Appellant contends that “[a]s discussed in the Saadeh Declaration, an
antimicrobial preservative is an agent that prevents degradation by bacteria
(i.e., prevents microbial contamination of the composition itself). However,
such teachings regarding antimicrobial preservatives are in stark contrast to
providing antimicrobial protection to safeguard against infection to a
patient.” Appeal Br. 25 (citing Saadeh Declaration 5); Reply Br. 3 (citing
Spec ¶ 23 (“that the terms ‘antibacterial’ and ‘antibiotic’ are specifically
defined [in the Specification] to refer to ‘substances or compounds that
destroy bacteria and/or viruses and/or inhibit the growth thereof via any
mechanism or route.’”)). Appellant contends that Domb supports this
position that “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. 25; see 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
‘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. In this definition, there is
no requirement that an antibiotic safeguards a patient from microbial
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infection. 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. ¶ 35. 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. Here, Domb teaches a “liposome
formulation [that] 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.’” FF11. We determine that this section of Domb identifies that
gentamicin and vancomycin has dual function as an antimicrobial and a
preservative. FF11. Tsao further supports the position that compounds can
act as both preservatives and antimicrobials, specifically identifying
polymyxin B sulfate as a strong cationic preservative. FF10. Tsao teaches
that preservatives can inhibit microbial growth as well as kill microbial
growth. FF10. 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. ¶ 42
(identifying polymyxin B sulfate as an antibiotic). Based on these teachings
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in the prior art, we agree with Examiner, given that “the function of a
preservative is to provide antimicrobial activity to the composition, and the
instant claims include vancomycin [, polymyxin B sulfate] or calcium
EDTA, the Examiner maintains that the claims do not necessarily exclude
preservatives from maintaining antimicrobial stability of the ophthalmic
composition.” Ans. 12.
We have considered the Saadeh Declaration but are not persuaded that
a product that prevents the degradation of the product itself (Saadeh
Declaration 5) cannot at the same time also reduce the incidence of local
bacterial infection associated with the application of the product to the
patient as suggested by Domb. See FF11. 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.
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.
(d) Motivation
Appellant contends that Kassem does not recognize that particle size
is important to prevent deactivation by moxifloxacin. While “Appellant may
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agree that, in general, Kassem may provide motivation for a suspension of
solid particles where all particles have a size of less than 10 microns” the
reference is silent with respect to including moxifloxacin. Appeal Br. 26. In
particular, Appellant contends that Kassem does not recognize that
“moxifloxacin’s tendency to deactivate many suspending agents resulting in
unacceptable coagulation, clumping and flocculation.” Appeal Br. 26.
We are not persuaded. MPEP 2144 (IV) states “the reason or
motivation to modify the reference may often suggest what the inventor has
done, but for a different purpose or to solve a different problem. It is not
necessary that the prior art suggest the combination to achieve the same
advantage or result discovered by Applicant. See, e.g., In re Kahn, 441 F.3d
977, 987 [] (Fed. Cir. 2006).”
Kassem teaches the production of nanosuspensions with nearly
insoluble glucocorticoid drugs, such as for example prednisolone, and
teaches that such nanosuspensions provide improved drug delivery. FF12.
Specifically, Kassem teaches that the nanosuspensions “exhibit a higher
intensity of drug action (expressed as IOPmax) and higher extent of drug
absorption (expressed as AUC).” FF12. Kassem concludes that
“[n]anosuspensions are effective in ophthalmic drug delivery allowing lower
doses and less frequent instillation. . . . Nanosuspensions, besides being
more convenient to the patient, would provide an alternative therapy with
fewer side effects.” FF12. Kassem, therefore, teaches that nanosuspensions
that have particle sizes of less than 10 µm are desirable because of increased
drug absorption and drug duration leading to less frequent applications.
Accordingly, we agree with Examiner that these teachings in Kassem
provide further motivation to use “particles at less than 10 microns as
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Kassem also suggests that this allows for administration of lower doses due
to the increased bioavailability of providing nanoparticulate size ranges, see
conclusion section.” Ans. 14.
2. Claims 2 and 6–12
With respect to these rejections, Appellant relies on the same
arguments relied upon with respect to claim 1, discussed above. See Appeal
Br. 27–29. 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 these claims as well.
C. Conclusion
We conclude that the preponderance of the evidence of record
supports Examiner’s conclusion that the combination of Cagle, Heier, Tsao,
Domb, Kassem, and Babu renders the composition of claims 1, 2, and 6–12
obvious. We thus affirm the rejection of claims 1, 2, and 6–12 under
35 U.S.C. § 103(a) as being obvious.
III. Obviousness over Cagle, Heier, Scott, Kassem, and Babu
Appellant does not provide separate arguments from those disclosed
with respect to claims 1, 2, and 6–12 relying on the combination of Cagle,
Heier, Kassem, and Babu as discussed above, see II.B. Appellant contends
“that because Scott is relied upon in support of the contention that calcium
EDTA is an alternative preservative for ophthalmic use, Scott fails to
overcome the above-discussed deficiencies of the Cagle modified by Heier,
Kassem and Babu.” Appeal Br. 31; Reply Br. 4.
Element (b4) of claim 35 recites “a pharmaceutically acceptable
carrier selected from the group consisting of edetate calcium disodium,
hydrochloric acid, sterile water and any combination thereof.” We interpret
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the “any combination thereof” as encompassing combinations that do not
require edetate calcium disodium. Examiner relies on Scott as showing that
edetate calcium disodium is a well-known preservative in the ophthalmic
acts. Ans.14, 18 (citing Scott ¶ 774); Final Act. 14. Because the claim as
construed does not require edetate calcium disodium, we find that there is no
need to rely on Scott for teaching that edetate calcium disodium is a
preservative. See generally In re Bush, 296 F.2d 491, 496 (CCPA 1961) (the
Board may rely on less than all of the references relied upon by the
Examiner).
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 35. As Appellant does not
argue the claims separately, the rejection of claims 35–41 is affirmed for the
same reasons discussed above with respect to claim 1 (see above II.B) as it
pertains to the teachings of Cagle, Heier, Kassem, and Babu.

DECISION SUMMARY
In summary:
Claim(s)
Rejected
35
U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1, 2,
6–12,
35–41
112 Indefiniteness 1, 2,
6–12,
35–41
1, 2,
6–12
103 Cagle, Heier, Tsao,
Domb, Kassem, Babu
1, 2,
6–12

35–41 103 Cagle, Heier, Scott,
Kassem, Babu
35–41
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Claim(s)
Rejected
35
U.S.C.
§
Reference(s)/Basis Affirmed Reversed
Outcome 1, 2,
6–12,
35–41

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