ARATANA THERAPEUTICS NV

Patent Trials and Appeals Board

Sep 18, 2020

2019007002 (P.T.A.B. Sep. 18, 2020)

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.
14/828,365 08/17/2015 Nesya GORIS ARA-23-USC 1941
50446 7590 09/18/2020
HOXIE & ASSOCIATES LLC
75 MAIN STREET
SUITE 203
MILLBURN, NJ 07041
EXAMINER
CABRAL, ROBERT S
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
09/18/2020 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):
HoxiePatentMail@gmail.com
HoxiePatentMail@hoxpat.com
file@hoxpat.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte NESYA GORIS, JOHAN NEYTS, ERWIN BLOMSMA,
STEFAAN WERA, AINOLA BILLIET, JOERI AUWERX,
VEERLE DEBEURME, MARYLINE ROE, and PASCAL PUIG1

Appeal 2019-007002
Application 14/828,365
Technology Center 1600
Before ERIC B. GRIMES, FRANCISCO C. PRATS, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims related to
an antiviral composition, which have been rejected as obvious. We have
jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.

1 Appellant identifies the real party in interest as Aratana Therapeutic Inc.
Appeal Br. 2. We use the word “Appellant” to refer to “applicant” as defined
in 37 C.F.R. § 1.42.
Appeal 2019-007002
Application 14/828,365

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STATEMENT OF THE CASE
“Different antiviral compounds are known for the treatment of herpes
virus infections. The compound 2-amino-9-[[(1S,2R)-1,2-bis(hydroxy-
methyl)cyclopropyl]methyl]-1,9-dihydro-6H-Purin-6-one (also known as
‘A-5021’) is a potent inhibitor of herpes virus replication.” Spec. 1:16–18.
“The present invention describes a method for solubilizing A-5021 under
isotonic and pH neutral conditions in concentrations between 1–10 mg/ml
(0.1 – 1% w/v), allowing the use of A-5021 in stable liquid formulations
such as eye-drops.” Id. at 2:1–3.
Claims 1–15 are on appeal. Claims 1 and 14, reproduced below, are
the independent claims:
1. A composition comprising:
- at least 0.1 % w/v 2-amino-9-[[(1S,2R)-1,2-bis(hydroxy-
methyl)cyclopropyl]methyl]1,9-dihydro-6H-Purin-6-one; and
- at least 15 % w/v of a cyclodextrin.
14. A method for preparing an ophthalmic solution, comprising
the steps of:
a) providing a solution comprising at least 10 % w/v
of a cyclodextrin;
b) adding 2-amino-9-[[(1S,2R)-1,2-bis(hydroxymethyl)
cyclopropyl]methyl]-1,9-dihydro-6H-Purin-6-one to said
solution;
c) solubilizing the 2-amino-9-[[(1S,2R)-1,2-
bis(hydroxymethyl)cyclopropyl]methyl]-1,9-dihydro-6H-
Purin-6-one added in step b);
d) repeating steps b) and c) until a concentration of
2-amino-9-[[(1S,2R)-1,2-bis(hydroxymethyl)cyclopropyl]
methyl]-1,9-dihydro-6H-Purin-6-one in said solution of at
least 1 mg/mL is obtained;
e) optionally, adding at least 0.008 mg/mL thiomersal.
Appeal 2019-007002
Application 14/828,365

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OPINION
Claims 1–15 stand rejected under 35 U.S.C. § 103 as obvious based
on Itahashi2 and Loftsson.3 Final Action4 5. The Examiner finds that
“Itahashi et al. teaches eye drops comprising 0.1% A-5021.” Id. The
Examiner acknowledges that Itahashi does not teach compositions
comprising a cyclodextrin, as claimed, but finds that Loftsson “teaches that
‘[c]yclodextrins have been added to aqueous eye drop preparations to
solubilize water-insoluble drug[s], to increase the chemical stability of
drugs, or to reduce local drug irritation in the eye.’” Id. The Examiner finds
that Loftsson also teaches that “‘optimum cyclodextrin concentration in
aqueous eye drop solutions is considered to be below about 15%’” and
reasons that “[b]elow about 15% would read on ‘at least 15 % w/w of
cyclodextrin.’” Id.
The Examiner concludes that it would have been obvious “to combine
the teaching of Itahashi et al. and Loftsson et al. and arrive at the instant
claims” because “an advantage or expected beneficial result . . . would have
been . . . to improve the stability of the active drug and[/]or reduce local
drug irritation of the eye.” Id.
Appellant argues that “Itahashi states ‘A-5021 eyedrops significantly
suppressed both corneal epithelial and stromal lesions at all concentrations
used.’ This statement in Itahashi casts doubt on the Examiner’s contention

2 Itahashi et al., “A-5021: a new acyclovir analogue inhibits murine herpetic
keratitis,” Cornea 27:334–338 (2008) (abstract only).
3 Loftsson et al., “Effect of Cyclodextrins on Topical Drug Delivery to the
Eye,” Drug Dev. Indus. Pharm. 23:473–481 (1997).
4 Office Action mailed April 19, 2018.
Appeal 2019-007002
Application 14/828,365

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that it would have been obvious to place the claimed active compound into a
composition with a cyclodextrin” because it “shows that A-5021 was able to
penetrate into corneal tissue in order to suppress herpetic lesions. The skilled
artisan, after learning of this quality, would not believe that A-5021 would
need to be placed into a cyclodextrin [composition] in order to show clinical
efficacy.” Appeal Br. 4–5.
Appellant also argues that “the Examiner has not demonstrated that
Loftsson teaches or suggests that cyclodextrin can solubilize or increase the
stability, for example, of any and all drugs, and that combining cyclodextrin
with A-5021 in a formulation would be expected to have any type of
predicted or expected effect.” Id. at 6.
In response to the Examiner’s statement that “Applicant admits in the
reply filed on 6/14/2017 at page 5, that the composition of Itahashi has ‘poor
stability,’ which would suggest the need to . . . incorporate Itahashi [sic,
Loftsson]” (Ans. 4), Appellant argues that the reply referred to the
Specification’s statement that Itahashi’s composition has poor stability.
Reply Br. 2. Thus, Appellant argues, “the Examiner has pegged the rejection
on impermissible hindsight reconstruction using information solely gleaned
from the Appellant’s specification to justify the rejection.” Id. at 3.
Appellant argues that “Itahashi . . . makes no statements as to the stability of
the composition.” Id.
We agree with Appellant that the Examiner has not shown that the
claimed composition would have been obvious to a skilled artisan based on
Itahashi and Loftsson. Itahashi describes a comparison of A-5021 eye drops
with acyclovir in treating corneal herpes simplex virus infections in mice.
Appeal 2019-007002
Application 14/828,365

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Itahashi, abstract. Itahashi reports that “[c]linical scores on the epithelium
and stroma treated with 0.1% A-5021 were equivalent to those with 3%
acyclovir treatment.” Id. Itahashi concludes that “A-5021 eyedrops, which
are easily applied onto the affected cornea, ameliorated clinical scores and
suppressed virus growth. It is a promising alternative treatment of herpetic
keratitis.” Id.
Loftsson states that “[c]yclodextrins have been added to aqueous eye
drop preparations to solubilize lipophilic water-insoluble drug[s], to increase
the chemical stability of drugs, or to reduce local drug irritation in the eye.”
Loftsson 473, abstract. The Examiner concludes that this disclosure would
have led a person of ordinary skill in the art to incorporate a “cyclodextrin
into the eye drop composition as taught by Itahashi et al. to improve the
stability of the active drug and[/]or reduce local drug irritation of the eye.”
Final Action 5.
However, as Appellant has pointed out (Reply Br. 3), Itahashi does
not describe its A-5021 composition as requiring improved stability. And,
although the Examiner states that “Applicant admits” that Itahashi’s
composition has poor stability (Ans. 4), Appellant correctly notes that the
statement relied on by the Examiner was summarizing what is stated in the
Specification, not in the prior art. See Response filed June 14, 2017, page 5.
Thus, the Examiner has not shown that a person of ordinary skill in the art
would have been aware, without the benefit of Appellant’s disclosure, of a
need to improve the stability of Itahashi’s composition.
The Examiner also cites “reduc[ing] local drug irritation of the eye” as
a reason to include a cyclodextrin in Itahashi’s composition. Final Action 5.
Appeal 2019-007002
Application 14/828,365

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However, the Examiner has not pointed to any evidence to show that
Itahashi’s eye drops caused any local drug irritation. Itahashi states that
“A-5021 eyedrops . . . are easily applied onto the affected cornea” and are “a
promising alternative treatment of herpetic keratitis.” Itahashi, abstract.
Thus, the evidence of record does not support combining a cyclodextrin with
Itahashi’s eye drops in order to reduce local drug irritation.
In summary, the Examiner has not shown, by evidence or sound
technical reasoning, that a person of ordinary skill in the art would have had
a reason to combine Loftsson’s cyclodextrin with Itahashi’s A-5021
composition. We therefore reverse the rejection of claims 1–15 under
35 U.S.C. § 103 based on Itahashi and Loftsson.
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1–15 103 Itahashi, Loftsson 1–15

REVERSED