Harrow IP, LLC

Patent Trials and Appeals Board

Nov 4, 2021

2020005812 (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.
14/972,822 12/17/2015 Ernesto Fernandez 109554-670702-0004-02-07 5488
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 ERNESTO FERNANDEZ and WILLIAM F. WILEY

Appeal 2020-005812
Application 14/972,822
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 December 17, 2015 (“Spec.”),
Final Office Action mailed March 8, 2019 (“Final Act.”); Appeal Brief filed
March 4, 2020 (“Appeal Br.”); Answer mailed May 22, 2020 (“Ans.”),
Reply Brief filed July 20, 2020 (“Reply Br.”), and Advisory Action mailed
July 29, 2020 (“Advisory Act.”).
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rejections of the claims as being obvious. We have jurisdiction under
35 U.S.C. § 6(b).
We AFFIRM.
STATEMENT OF THE CASE
Claims 1–6, 8, 10, 12, 28, 32–38, 413 and 42 are on appeal,4 and can
be found in the Claims Appendix of the Appeal Brief. Claim 1, the sole
independent claim, is representative of the claims on appeal, and reads as
follows:
1. An ophthalmological pharmaceutical composition, consisting
of:
(a) a therapeutic component consisting of:
(a1) 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 or N-oxides thereof; and
(a2) a therapeutically effective quantity of a
corticosteroid independently selected from the group
consisting of prednisone, prednisolone,
methylprednisone, corticol, cortisone,
fluorocortisone, deoxycorticosterone acetate,
aldosterone, budesonide, and pharmaceutically

3 Claim 40 is listed in the Final Office Action as rejected under 35 U.S.C.
§ 112(b), this rejection, however, was withdrawn by Examiner in the
Advisory Action. Claim 40 is still pending (see Appeal Br. 5 (listing
dependent claims), 40 (Claims Appendix)), but we note that there is
currently no rejection applied to this claim. In the event of further
prosecution Examiner is encourage to clarify the status of this claim.
4 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. 2020-005442 (Application Number 15/057,711)
and Appeal No. 2020-005499 (Application Number 15/061,488).
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acceptable salts, hydrates, solvates, ethers, esters,
acetals and ketals thereof;
(b) a pharmaceutically acceptable solubilizing and suspending
agent selected from the group consisting of non-ionic
polyoxyethlene-polyoxypropylene block copolymers,
wherein the non-ionic polyoxyethlene-polyoxypropylene
block copolymer is at a concentration of about 0.01
mass% to 10.0 mass%;
(c) a therapeutically effective quantity of an antibiotic
selected from the group consisting of vancomycin,
teicoplanin, telavancin, decaplanin, ramoplanin,
gentamicin, tobramycin, amikacin, cefuroxime,
polymyxin B sulfate, trimethoprim, and a combination
thereof; and
(d) a pharmaceutically acceptable carrier therefor, wherein
the carrier is sterile water,
wherein the ophthalmological pharmaceutical composition is a
suspension consisting of particles formed by components (a),
(b), and (c), wherein about 99% of all the particles have a
diameter of 5 μM or less, the composition loses no potency and
maintains stability after about six months of storage, and is
formulated in the form of eye drops having a viscosity suitable
for administration via an eyedropper for treating an
ophthalmological disease, condition or pathology in a
mammalian subject.
Appeal Br. 32 (Claims Appendix).
REJECTIONS
Appellant requests review of the following grounds of rejection made
by Examiner:
I. Claims 1–6, 10, 12, and 32–38 under 35 U.S.C. §103 over
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Cagle5 in view of Charles,6 Domb,7 Huerva,8 and
Kulshreshtha;9and
II. Claims 28 under 35 U.S.C. §103 over Cagle in view of Charles,
Domb, Huerva, and Kulshreshtha and further in view of
Sponsel;10 and
III. Claims 8, 41, and 42 under 35 U.S.C. §103 over Cagle in view
of Charles, Domb, Huerva, and Kulshreshtha and further in
view of Babu.11

I. Obviousness over Cagle, Charles, Domb, Huerva, 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

5 Cagle et al. US 2002/0193370 A1, published Dec. 19, 2002 (“Cagle”).
6 David Marcus & Charles Riffkin, US 3,138,528, issued June 23, 1964
(“Charles”).
7 Domb et al., US 5, 227,165, issued July 13, 1993 (“Domb”).
8 Huerva et al., Levels o of Vanco1nycin in Aqueous Humor After Topical
Eye Drops Administration, 9 J. OCULAR PHARM. 167–170 (1993)
(“Huerva”).
9 Kulshreshtha et al., US 5,803,966, issued Sept. 8, 1998 (“Kulshreshtha”).
10 Sponsel et al., US 2004/0198829 Al, published Oct. 7, 2004 (“Sponsel”).
11 Babu et al., US 2007/0049552 A1, published Mar. 1, 2007 (“Babu”).
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of one or more antibiotics with the anti-inflammatory activity of
one or more steroid or non-steroid agents in a single
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 % 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 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-
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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
4.5–8.0 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. Charles teaches ophthalmic administration of steroids such as
hydrocortisone, cortisone, prednisolone, prednisone,
triamcinolone, among others. See Charles 1:35–38.
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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 a suspension, and also include “antimicrobials 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. Huerva teaches the use of the antibiotic vancomycin in eye
drops. Huerva, Abstract, see also id. at 168 (Material and
Methods) (eye drops have a final concentration of 30–33 mg/ml
of vancomycin). Huerva teaches that “[t]he growth of the
majority of Gram positive germs is inhibited with a
concentration of 0.1 µg/ml of Vancomycin.” Id. at 167. “[T]he
minimum inhibitory concentrations of Vancomycin for
Staphilococcus [sic] epidermis are 0.4 µg/ml.” Huerva 169.
Huerva teaches that instilling one drop onto the eye yielded a
concentration of vancomycin in the aqueous humor of
0.52 µg/ml. Id. at 168 (Figure 1).
FF12. Kulshreshtha teaches the production of prednisolone acetate
particles having an “[a]verage particle sizes of about 1 μm or
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less (number average) and narrow particle size ranges are
obtainable.” Kulshreshtha, Abstract. “[S]uspensions of particles
of about 1 μm or less possess superior particulate stability due
to the colloidal nature of the smaller particles.” Id. at 1:18–21.
Prednisolone acetate sizing processes according to
Kulshreshtha produces “average particle sizes of about 1 μm or
less, a narrow particle size distribution with no particles greater
than about 10 μm, and a particle size index of less than 4.” Id. at
6:57–62.
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 Cagle teaches the use of one or more anti-
inflammatories. Final Act. 5; FF3–FF5. 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 teaches that the “solubility of the composition can be enhanced by
surfactants including polyoxyethylene/polyoxypropylene surfactants (i.e.
poloxamers) present in amounts from 0.01-2% by weight.” Final Act. 6;
FF8.
Examiner acknowledges that Cagle does not teach the elected
corticosteroid – prednisone. Final Act. 6. Examiner looks to Charles for
teaching “ophthalmic compositions which contain actives including
prednisone or triamcinolone or prednisolone corticosteroids.” Final Act. 6;
FF9. Examiner concludes that based on the combined teachings, “[i]t would
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9
have been prima facie obvious to a person of ordinary skill in the art before
the time of filing to substitute the corticosteroids disclosed in Cagle for
prednisone.” Final Act. 6 (citing MPEP 2144.06).
Examiner finds that Cagle suggests including preservatives in the
range of 0.001% to 1.0%, but does not teach antibiotics, such as
vancomycin, as being a preservative. Final Act. 6. Examiner looks to Domb
for teaching “that antimicrobial agents such as vancomycin also functions as
a preservative in that it reduces bacteria.” Final Act. 6; FF10. Based on these
combined teachings, Examiner concludes that it would have been prima
facie obvious to a person of ordinary skill in the art “to provide Cagle’s
ophthalmic composition with the antibiotic vancomycin. . . . [Because]
Cagle’s composition may contain preservatives and vancomycin is known
[to function] as a preservative [and] antimicrobial compound.” Final Act. 7.
Alternatively, Examiner concludes that it would be obvious to “combine two
compositions known in the art useful in forming eye drops and for treating
antimicrobial infections [to form a third composition] with a reasonable
expectation of success as Cagle and Huerva are both directed to ophthalmic
eye drop compositions.” Final Act. 7.
Examiner acknowledges that Cagle teaches suspensions but does not
teach a particle size for the steroid suspension and looks to the teaching of
Kulshreshtha for disclosing prednisolone acetate particles having a size of
1 µm or less and providing a reason why this size is desirable. Final Act. 8;
see also FF12 (“[S]uspensions of particles of about 1 μm or less possess
superior particulate stability due to the colloidal nature of the smaller
particles.”). Based on the combined teachings of the references, Examiner
concludes that it would have been prima facie obvious to provide the
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corticosteroid of Cagle in particle form having a 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 because as taught by Kulshreshtha smaller particle sizes
not only reduce ocular irritation but also provide superior particulate
stability and enhanced bioavailability.” 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 the Examiner’s responses to Appellant’s arguments. We
address Appellant’s contentions below.
(a) Antimicrobial and preservative agents
Appellant contends that “the compositions of Cagle include at least
trace amounts of a preservative” and that the claims based on the “consisting
of” language exclude preservatives. Appeal Br. 20 (citing Saadeh12
Declaration).
Appellant respectfully submits that while Domb does disclose
that the formulation can contain antimicrobial agents or
preservatives to reduce the incidence of local bacterial
infections (Domb at col. 5, 11. 18-20), the very next sentence
gives a reference for examples of stable preservatives that may
be used. Domb at col. 5, 11. 21-24. Likewise, Domb provides a
list of biologically active materials, which includes
antimicrobials but excludes preservatives, that may be
encapsulated in the lipospheres. (Domb at col. 9, 11. 4-8). Since
one of skill in the art reading Domb would clearly understand

12 Declaration under 37 C.F.R. § 1.132 by Dr. Dennis Saadeh, submitted on
June 21, 2018 (“Saadeh Declaration”).
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that the antimicrobials and preservatives of Domb are not
interchangeable, Appellant respectfully submits that Domb fails
to cure the above-discussed deficiencies of Cagle and Charles.
Appeal Br. 21.
According to Appellant “Huerva is absolutely silent with regard to use
of vancomycin as a preservative.” Id.
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. ¶ 22. 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.
¶ 36. 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.” Accordingly, a compound
that would prevent the growth of bacteria would at the same time also
prevent degradation by the bacteria because the bacteria are not actively
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
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infections associated with lipid-based injections.’” FF11. Here, Domb
identifies gentamicin and vancomycin as having dual function as an
antimicrobial and a preservative. Examiner explains that “[i]t would have
been prima facie obvious to a person of ordinary skill in the art to provide
Cagle’s ophthalmic composition with the antibiotic vancomycin. . . .
[Because] Cagle’s composition may contain preservatives13 and vancomycin
is known [to function] as a preservative [and] antimicrobial compound.”
Final Act. 7. Huerva also suggests the inclusion of the antibiotic vancomycin
in eye drops. FF11. Huerva explains that concentrations as low as 0.1 µg/ml
of vancomycin inhibits the growth of gram positive bacteria, a primary
target of vancomycin. FF11. The teaching in Huerva supports a finding that
vancomycin inhibits the growth of bacteria once instilled onto the eye of a
patient. FF11. The concentration of vancomycin in the eyedrop would also
be sufficient to inhibit bacterial growth that is inadvertently introduced into a
multi-dose container. Accordingly, we agree with Examiner,
given [that] Cagle teaches the composition can contain a
preservative in order to provide antimicrobial protection to the
product, and the prior art suggests that antibiotics also function
as preservatives in that they provide antimicrobial activity, it
would have been obvious to substitute the antimicrobial
preservative of Cagle for vancomycin which is taught to
provide antimicrobial reduction of bacteria. Cagle renders this
obvious because Cagle expressly suggest any other known
agent can be supplement to provide microbial contamination.

13 The Specification identifies glycopeptide antibiotics as including
polymyxin B sulfate. Spec. ¶ 46. Tsao relied on in related appeals
2020-005442 and 2020-005444 describes polymyxin B sulfate to also
function as a preservative. See Tsao 448–55 ((“Strong cationic preservatives
include, without limitation thereto, polymyxin B sulfate, . . . benzalkonium
chloride, . . . and mixtures thereof.”).
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Ans. 5.
Appellant provides the Saadeh Declaration to support the position that
Cagle’s solution incorporate preservative. Appeal Br. 20 (citing Saadeh
Declaration 2–3). We have considered Appellant’s argument and reviewed
the supporting Saadeh Declaration but are not persuaded that they are
sufficient, when considered together with the evidence of obviousness, to
establish non-obviousness. The point is not that Cagle’s multi-dose solution
incorporates what Cagle identifies as a preservative. Examiner
acknowledges that Cagle does not disclose vancomycin or any other
antibiotic as a preservative. Examiner finds, however, that vancomycin can
act as a preservative to protect the product from bacterial growth and also as
an antibiotic to reduce bacterial growth on tissue. See Ans. 5 (Preservative
“refers to any substance which is added to prevent decomposition due to
chemical or bacterial action.”), see also id. at 5–6 (“[B]ecause antimicrobial
agents act to reduce or inhibit bacteria, the instantly claimed composition
also does have preservative agents present.”), id. at 10 (“Huerva provides
further motivation for selecting vancomycin as the antimicrobial
preservative with the eye drops because vancomycin also possesses superior
antimicrobial activity since it is able to penetrate infections caused by gram
positive bacteria of the anterior segment.”). Appellant has not provided
evidence that vancomycin at concentrations disclosed in Huerva would not
function as both an antibiotic and preservative. See Ans. 10–11.
Accordingly, we agree with Examiner that the claims do not exclude
preservatives that function as antimicrobial compounds and are added to the
composition for their antimicrobial activity. See Ans. 6.
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The evidence of record supports Examiner’s conclusion that the
combination of references teach an eye drop composition containing
vancomycin that functions simultaneously as an antimicrobial and
preservative and thereby supports Examiner’s conclusion that it would be
obvious to substitute Cagle’s preservative for Domb’s or Huerva’s
vancomycin.
(b) Long felt need
Appellant contends that there was long felt and unmet need for
combination therapy. Appellant relies on the Wiley14 Declaration to support
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

14 Declaration under 37 C.F.R. § 1.132 by Dr. William Wiley submitted
July 21, 2018 (“Wiley Declaration”).
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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
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 evidence in the declaration
of long felt need is unpersuasive because “Cagle already establishes
compositions which are combined for a single composition and being
capable of use[] with one vial.” Ans. 7; FF3. In other words, Cagle provides
the instructions for solving the problem of administering antibiotics and one
or more anti-inflammatory agents as a single composition. 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 for the following reasons.” Wiley Declaration 2,
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 in separate vials
over an extended period of time with waiting periods between administering
the individual drops does not provide evidence that an art-recognized
problem existed for a long period of time without solution. See Wiley
Declaration 2–3. The fact that combination therapies are not presently used
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and are 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 provides anti-infective
activity of one or more antibiotics with the anti-inflammatory agents. FF1,
FF3. Thus, Cagle supplies the key element of including multiple actives in
one composition. Accordingly, Appellant’s contention does not persuade us
that Examiner erred.
(c) Reasonable expectation of success
Appellant contends the Specification describes the difficulty of
obtaining a stable suspension because “moxifloxacin’s tendency to
deactivate many suspending agents resulting in unacceptable coagulation,
clumping and flocculation.” Appeal Br. 22. In particular, Appellant contends
“that selecting the appropriate excipient for use in the pharmaceutical
formulations ensures that the corticosteroid ‘safely forms a stable suspension
even when moxifloxacin is also present in the same formulation.’” Id. (citing
Spec. ¶ 52).
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).”
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Examiner finds that “Kulshreshtha makes it known to an ordinary
skilled artisan that particle sizes for ophthalmic suspension must be less than
10 microns to reduce irritation, with smaller particles sizes being preferable
due to enhanced bioavailability. Suspensions with their particles of about
1 micron in size have superior particulate stability.” Ans. 11–12; FF12.
“Similarly, Cagle also discloses that the solubility of the composition is
enhanced by excipients including polyoxyethylene-polyoxypropylene block
copolymers (also known as Pluronic or Poloxamer).” Ans. 13 (citing Cagle
¶ 41; FF8). In addition, Examiner finds that one of ordinary skill in the art
would have included vancomycin in Cagle as providing the benefit of
protecting against bacteria because vancomycin is known to reduce bacteria.
Ans. 14, see also id. at 10 (“Huerva provides further motivation for selecting
vancomycin as the antimicrobial preservative with the eye drops because
vancomycin also possesses superior antimicrobial activity since it is able to
penetrate infections caused by gram positive bacteria of the anterior
segment.”); see FF10–FF11. We agree with Examiner that combined, the
references provide sufficient reason for making the combination to arrive at
the claimed invention. “Obviousness does not require absolute predictability
of success . . . all that is required is a reasonable expectation of success.” In
re Droge, 695 F.3d 1334, 1338 (Fed. Cir. 2012) (quoting In re Kubin, 561
F.3d 1351, 1360 (Fed. Cir. 2009) (citing In re O’Farrell, 853 F.2d 894, 903-
04 (Fed.Cir.1988)).
2. Claims 2–6, 10, 12, and 32–38
With respect to these rejections, Appellant relies on the same
arguments relied upon with respect to claim 1. See Appeal Br. 24–28. For
the reasons discussed above, we find that Examiner has established a prima
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facie showing of obviousness with respect to claim 1. Accordingly, we
affirm the rejection of claims 2–6, 10, 12, and 32–38 as well.
C. Conclusion
We conclude that the preponderance of the evidence of record
supports Examiner’s conclusion that the combination of Cagle, Charles,
Domb, Huerva, and Kulshreshtha renders the composition of claim 1
obvious. We thus affirm the rejection of claims 1–6, 10, 12, and 32–38 under
35 U.S.C. § 103(a) as being obvious.
II. Obviousness over Cagle, Charles, Domb, Huerva, Kulshreshtha, and
Sponsel
Appellant contends “that Sponsel teaches that ‘[u]nder ordinary
conditions of storage and use, these preparations contain a preservative to
prevent the growth of microorganisms.’ (Sponsel at paragraph [0204]).”
Appeal Br.28–29. Therefore, the inclusion of Sponsel with the combination
of Cagle, Charles, Domb, Huerva, and Kulshreshtha further supports that
liquid compositions for use in the eye require preservatives. Id.
Claim 28 recites: A pharmaceutical kit, comprising a sealed container
containing the pharmaceutical composition of claim 1, and an instruction for
use of the composition enclosed with the container.
Examiner relies on Sponsel for teaching supplying the composition in
the form of a kit.
Kits of the invention generally comprise, in at least a first
suitable container, a therapeutically effective combination of at
least a first prostanoid and at least a first biological, diagnostic
or therapeutic agent, including an ophthalmically active
biological agent. The prostanoid and other agent may be
comprised within a single container or within distinct
containers in the kit.
Sponsel ¶ 87.
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Where the difference between a claimed invention and the prior art
consists of the content of printed matter, the printed matter must create a
“new and unobvious functional relationship” in order to patentably
distinguish the claimed product from the prior art. See In re Ngai, 367 F.3d
1336, 1338 (Fed. Cir. 2004) (adding printed instructions describing a new
use for a kit composed of old materials did not distinguish the claimed kit
from the prior art).
We are not persuaded by Appellant’s contention that Sponsel supports
that liquid composition require preservatives. Here, Appellant’s are not
addressing the combination as articulated by Examiner that relies on Sponsel
for teaching a kit to supply an ophthalmically active biological agent in “a
sealed container to minimize contamination and spill.” Final Act. 9.
Appellant’s response, therefore, does not address Examiner’s reason that it
would have been obvious to provide instruction on how the kit is to be used.
See id. at 10.
We conclude that the preponderance of the evidence of record
supports Examiner’s conclusion that the combination of Cagle, Charles,
Domb, Huerva, Kulshreshtha, and Sponsel renders the kit of claim 28
obvious. We thus affirm the rejection of claim 28 under 35 U.S.C. § 103(a)
as being obvious.
III. Obviousness over Cagle, Charles, Domb, Huerva, 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)
FF13. Babu teaches pharmaceutical compositions comprising a
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fluroquinolone 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 ¶ 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.”).
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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.”).
f) The pharmaceutical composition also contains water to
balance and has a pH between 4 and 7. Babu claim 1.
B. Analysis
1. Claim 8
Appellant contends that “Babu includes at least one preservative in an
amount of 0.001% to 2% by weight of the formulation,” therefore, further
supporting Appellant’s assertion that one of ordinary skill in the art at the
time the invention was made “would have understood that liquid
compositions suitable for use in the eye require preservatives.” Appeal
Br. 30 (citing Saadeh Declaration 4–5).
We do not find Appellant’s’ arguments persuasive. As an initial
matter, we note that Appellant’s arguments attacking the references
individually (see, e.g., Appeal Br. 29–30), where the rejection is based on
their combination, is improper. In re Keller, 642 F.2d 413, 426 (CCPA
1981). Appellant is not addressing the rejection as articulated by Examiner.
Specifically, Examiner reiterates that Babu was cited to establish that the
concentration of “polyoxyethylene-polyoxypropylene block copolymer,
moxifloxacin, and corticosteroid” for use in an ophthalmic formulation. Ans.
15. Examiner maintains, and we agree, that Appellant’s claim does not
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exclude compounds such as vancomycin that can function as both a
preservative and an antimicrobial. See Ans. 16; see above I.B.1.a.
2. Claims 41 and 42
With respect to these rejections, Appellant relies on the same
arguments relied upon with respect to claim 8. See Appeal Br. 30–31. For
the reasons discussed above, we find that Examiner has established a prima
facie case showing of obviousness with respect to claim 8. Accordingly, we
affirm the rejection of claims 41 and 42 as well.
A. Conclusion
We conclude that the preponderance of the evidence of record
supports Examiner’s conclusion that the combination of Cagle, Charles,
Domb, Huerva, Kulshreshtha, and Babu renders the composition of claim 8
obvious. We thus affirm the rejection of claim claims 8, 41, and 42 under
35 U.S.C. § 103(a) as being obvious.

DECISION SUMMARY
In summary:
Claim(s)
Rejected
35 U.S.C.
§
Reference(s)/Basis  Affirmed Reversed
1–6, 10, 12,
32–38
103 Cagle, Charles, Domb,
Huerva, Kulshreshtha 
1–6, 10,
12,
32–38

28 103 Cagle, Charles, Domb,
Huerva, Kulshreshtha,
Sponsel 
28
8, 41, 42 103 Cagle, Charles, Domb,
Huerva, Kulshreshtha,
Babu
8, 41, 42
Overall
Outcome
1–6, 8,
10, 12,
28,

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Claim(s)
Rejected
35 U.S.C.
§
Reference(s)/Basis  Affirmed Reversed
32–38,
41, 42

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