THE BOARD OF TRUSTEES OF THE¿UNIVERSITY OF ILLINOIS

Patent Trials and Appeals Board

Aug 26, 2020

15527103 - (D) (P.T.A.B. Aug. 26, 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.
15/527,103 05/16/2017 Anantha Harijith UIC0050US.NP 2718
26259 7590 08/26/2020
LICATA & TYRRELL P.C.
66 E. MAIN STREET
MARLTON, NJ 08053
EXAMINER
FAY, ZOHREH A
ART UNIT PAPER NUMBER
1617
NOTIFICATION DATE DELIVERY MODE
08/26/2020 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):
PTOactions@licataandtyrrell.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte ANANTHA HARIJITH, VISWANATHAN NATARAJAN,
ROBERTO F. MACHADO, and JEFFREY JACOBSON
__________

Appeal 2020-001340
Application1 15/527,103
Technology Center 1600
__________

Before DONALD E. ADAMS, RICHARD M. LEBOVITZ, and
RACHEL H. TOWNSEND, Administrative Patent Judges.

TOWNSEND, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method of treating a pulmonary disease or condition, which have been
rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
STATEMENT OF THE CASE
Appellant’s Specification indicates that there is a known “correlation
between sphingosine kinase (SphK) activity and lung injury.” (Spec. ¶ 4.)
For example “increased expression of sphingosine kinase 1 (SphKl) has

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the real party in interest as The Board of
Trustees of the University of Illinois. (Appeal Br. 1.)
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Application 15/527,103

2
been found in lung tissues from patients with idiopathic pulmonary fibrosis.”
(Id.)
The Specification also states that selective inhibitors of SphK1 are
known in the prior art. (Id. ¶ 5.) Appellant’s invention is directed at treating
pulmonary diseases or conditions with a selective SphK1 inhibitor having
20-fold greater selectivity for SphK1 than SphK2 and a 50% inhibition at
less than 10 μM. (Id. ¶6.)
Claims 1–5 and 11–13 are on appeal.2 Claim 1 is illustrative and
reads as follows:
1. A method of treating a pulmonary disease or condition
in a subject comprising administering to a subject in need of
treatment an effective amount of a SphKl inhibitor to treat the
subject’s pulmonary disease or condition, wherein the SphKl
inhibitor
(a) exhibits at least a 20-fold greater selectivity for SphKl
than SphK2; and
(b) is cell permeable, has an IC50 value of less than
10 μM, or has a Ki of less than 10 μM, or a combination
thereof.
(Appeal Br. 16.)

2 Claims 6–8 remain pending, but are withdrawn from consideration.
Appeal 2020-001340
Application 15/527,103

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The prior art relied upon by the Examiner is:
Name Reference Date
Santos et al. WO2013/119946 A1 Aug. 15, 2013
Mark E. Schnute et al., Modulation of cellular S1P levels with a novel,
potent and specific inhibitor of sphingosine kinase-1, 444 Biochem J., 79–
88 (2012).
The following ground of rejection by the Examiner is before us on
review:
Claims 1–5 and 11–13 under 35 U.S.C. § 103(a) as unpatentable over
Santos and Schnute.
DISCUSSION
The Examiner finds that Santos teaches administering “an effective
amount of a SphK1 inhibitor to prevent or treat [a] subject’s pulmonary
disease or condition.” (Final Action 6.) The Examiner further finds that
Santos teaches “the SphK1 inhibitor is cell permeable and has a . . . [Ki] of
less than 10 μm (para [0130[]]), Table 2, pg 46, Compound 64, . . .
Compound 64 of the invention is a potent and selective Inhibitor of
SphK1).” (Id.)
The Examiner finds that Santos does not teach the SphK1 inhibitor to
be PF-543 (the compound recited in claims 3 and 11). (Id.) The Examiner
concludes, however, that substituting Compound 64 of Santos with PF-543
would have been obvious in light of the teachings of Schnute. (Id. at 6–7.)
In particular, the Examiner finds that Schnute teaches PF-543 is “a potent
and selective inhibitor of SphK1 activity” and as such substitution of PF-543
for Compound 64 would have been obvious “to enhance the efficacy of
inhibiting SphK1 activity and to thereby improve therapeutic efficacy of
treating a pulmonary disease in a subject.” (Id.)
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Application 15/527,103

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We disagree with the Examiner’s factual findings and conclusion that
the claims are obvious over Santos and Schnute. In particular, we disagree
that Santos teaches treating a pulmonary disease or condition with a
selective SphK1 inhibitor. As Appellant notes, Santos is directed to using
compounds of formula 1 for treating a myriad of diseases or conditions.
(See Appeal Br. 12; Reply Br. 2; Santos ¶¶ 15, 36, 37.) Those conditions
include neoplastic diseases (Santos ¶ 39), diseases that involves excess
vascular growth, such as macular degeneration (id. ¶ 40), inflammatory
diseases (id. ¶¶ 42–43), allergic diseases (id. ¶ 41), sepsis (id. ¶ 46), as well
as fibrotic diseases, such as pulmonary fibrosis (id. ¶ 45).
Compounds of formula I are required to be SphK enzyme inhibitors,
but not necessarily selective SphK1 inhibitors as required by the claims.
They may “have activity as selective inhibitors of the SphKl enzyme or the
SphK2 enzyme or have activity as inhibitors of both SphKl and SphK2
enzymes.” (Santos ¶ 37.)
It is true that Santos teaches Compound 64 selectively inhibits SphK1,
decreasing S1P. (Id. ¶¶ 130 Table 2, 575.) However, Santos teaches a
number of other compounds for use in treating any one of the identified
diseases or conditions including, as Appellant explained, compound
SLR080811 (Appeal Br. 12), which is an SphK2-selective inhibitor and
increases S1P levels. (Santos ¶¶ 573–574, ¶ 57 (noting “compound (S)-2-(3-
(4-octylphenyl)-1,2,4-oxadiazol-5-YL)pyrrolidine-1-carboximidamide
(SLR080811)”); ¶ 130 Table 2 (noting compound (S)-2-(3-(4-octylphenyl)-
1,2,4-oxadiazol-5-YL)pyrrolidine-1-carboximidamide is compound 49).)
Furthermore, Santos links pulmonary fibrosis treatment and
compounds of Formula 1 that have activity to “improve the barrier function
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Application 15/527,103

5
of endothelial cells, which are identified as compounds “of Formula 1 that
inhibit[] SphK2 enzymatic activity.” (Id. ¶ 48.) The Examiner did not
identify disclosure in Santos that ties the use of a selective inhibitor of the
SphKl enzyme as opposed to a selective inhibitor of the SphK2 enzyme for
treating a pulmonary condition.
Thus, we do not agree with the Examiner that Santos teaches the use
of compound 64, which is an SphK1 selective inhibitor, for use in treating
pulmonary disease. Instead, we find the Examiner’s position that Santos
teaches compound 64 for treating a pulmonary condition amounts to an
impermissible application of obvious to try. Nothing in Santos that we have
been guided to indicates that SphK1 inhibition is critical for treating
pulmonary conditions or provides any suggestion that compound 64 would
be likely to be successful in treating pulmonary conditions as opposed to one
of the other myriad conditions mentioned. In re Kubin, 561 F.3d 1351, 1359
(Fed. Cir. 2009) (identifying two categories of obvious-to-try situations that
do not equate to prima facie obviousness under § 103: when what was
“obvious to try” was (a) to vary all parameters or try every available option
until one succeeds, where the prior art gave no indication of critical
parameters and no direction as to which of many possibilities is likely to be
successful; or (b) to explore a new technology or general approach in a
seemingly promising field of experimentation, where the prior art gave only
general guidance as to the particular form or method of achieving the
claimed invention.).
We also agree with Appellant that the Examiner has not adequately
established a reason that it would have been obvious to substitute PF-543 for
compound 64 to treat a pulmonary condition. (Appeal Br. 12–13; Reply Br.
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3.) Schnute determines “PF-543 is the most potent inhibitor of SphK1
described to date.” (Schnute Abs.) However, the Examiner did not identify
any teaching in Schnute to tie this fact to a reasonable expectation that this
compound would be able to treat pulmonary conditions. Schnute does not
attribute any treatment capabilities with this compound, despite recognizing
that
inhibitors of SphKl could potentially lead to the development of
novel strategies for the treatment of autoimmune diseases, for
cancer therapy and for neurodegenerative diseases.
(Id. at 85.) In fact, Schnute notes, with regard to the cancer cell line 1483 in
which the compound was tested, that despite inhibiting SphK1 to a great
extent, the cancer cell line grew at the normal rate. (Id. at 87.) Schnute also
was also “unable to confirm growth inhibition by blockade of SphKl activity
in U937 [leukemia] and LN229 [glioblastoma] cells.” (Id.) After
performing various experiments, Schnute concludes only that PF-543
“provides a new and valuable tool for the interrogation of biological effects
of modulation of S1P signaling resulting from specific inhibition of SphK 1
catalytic activity.” (Id. at 87.)
For the foregoing reasons, we do not affirm the Examiner’s rejection
of claims 1–5 and 11–13 as being obvious from Santos and Schnute.
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1–5, 11–13 103 Santos, Schnute 1–5, 11–13

REVERSED