Emory University

Patent Trials and Appeals Board

Apr 6, 2020

15303481 - (D) (P.T.A.B. Apr. 6, 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.
15/303,481 10/11/2016 Keqiang Ye 14047 US 6412
81100 7590 04/06/2020
Patent Manager
Emory University - Office of Tech Transfer
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1599-001-1AZ
Atlanta, GA 30322
EXAMINER
SCHMITT, MICHAEL J
ART UNIT PAPER NUMBER
1629
NOTIFICATION DATE DELIVERY MODE
04/06/2020 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):
krebel@emory.edu
ottip@emory.edu
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte KEQIANG YE, HAIAN FU, and YUHONG DU
____________

Appeal 2020-000259
Application 15/303,481
Technology Center 1600
____________

Before DONALD E. ADAMS, RICHARD M. LEBOVITZ, and
FRANCISCO C. PRATS, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from Examiner’s
decision to reject claims 7–9 (Final Act.2 2). We have jurisdiction under
35 U.S.C. § 6(b).
We REVERSE.

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 “Emory
University” (Appellant’s April 1, 2019 Appeal Brief (Appeal Br.) 3).
2 Examiner’s June 29, 2018 Final Office Action.
Appeal 2020-000259
Application 15/303,481

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STATEMENT OF THE CASE
Appellant’s “disclosure relates to asparagine endopeptidase inhibitors
for managing cancer and compositions related thereto” (Spec. 2: 26–27).
Claim 7 is reproduced below:
7. A pharmaceutical composition comprising 7-(3-(4-
chlorophenoxy)-2-hydroxypropyl)-8-mercapto-3-methyl-3,7-
dihydro-1H-purine-2,6-dione or salts thereof and a
pharmaceutically acceptable excipient.
(Appeal Br. 20.)
Ground of rejection before this Panel for review:
Claims 7–9 stand rejected under 35 U.S.C. § 103(a) as unpatentable
over the combination of STN3 and Yamazaki.4
ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
FACTUAL FINDINGS (FF)
FF 1. Examiner finds that STN discloses “7-(3-(4-chlorophenoxy)-2-
hydroxypropyl)-8-mercapto-3-methyl-3,7-dihydro-1H-purine-2,6-dione,”
which has the formula:

(Ans. 3; see STN.)

3 STN entry for CAS Reg. No. 331675-23-1 (Apr. 17, 2001).
4 Kazuto Yamazaki et al., Identification of phosphodiesterase-1 and 5 dual
inhibitors by a ligand-based virtual screening optimized for lead evolution,
16 Bioorganic & Medicinal Chemistry Letters 1371–79 (2006).
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FF 2. Examiner finds that STN fails to disclose 7-(3-(4-chlorophenoxy)-2-
hydroxypropyl)-8-mercapto-3-methyl-3,7-dihydro-1H-purine-2,6-dione in
combination “with a pharmaceutically acceptable excipient” (Ans. 4; see
STN).
FF 3. Yamazaki discloses the “[i]dentification of phosphodiesterase-1 and
5 dual inhibitors by a ligand-based virtual screening optimized for lead
evolution” (Yamazaki, Title; see id. at 1371 (Yamazaki discloses that
“virtual screening is expected to increase the success rate [of lead compound
discovery] through identification of multiple and diverse lead
candidates . . . with a novel scaffold”); see Ans. 5).
FF 4. Yamazaki’s method identified seven lead compounds that “showed
inhibitory activities against both PDE-1 and 5,” including compounds 29 and
35 having the formulas:
Compound 29:

Compound 35:

(Yamazaki 1374–1375; see also id. at 1376, Table 3; see also Ans. 5–6.)
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FF 5. Examiner finds that Yamazaki’s compound 35 is structurally similar
to the compound of Appellant’s claimed invention, varying only with respect
to a naphthyl instead of a chlorophenyl (Ans. 6).
FF 6. Yamazaki discloses that “inhibitors of PDE-1 and 5 are expected as
therapeutics for cardiovascular diseases, such as hypertension, angina,
cardiac failure, and obstructive arteriosclerosis” (Yamazaki 1371; see Ans.
6).
FF 7. Examiner finds that Appellant
does not define [the term] excipient, though in the
pharmaceutical arena one generally thinks of “an excipient [a]s
a substance formulated alongside the active ingredient of a
medication, included for the purpose of long-term stabilization,
bulking up solid formulations that contain potent active
ingredients in small amounts (thus often referred to as ‘bulking
agents’, ‘fillers’, or ‘diluents’), or to confer a therapeutic
enhancement on the active ingredient in the final dosage form,
such as facilitating drug absorption, reducing viscosity, or
enhancing solubility. Excipients can also be useful in the
manufacturing process, to aid in the handling of the active
substance concerns such as by facilitating powder flowability or
non-stick properties, in addition to aiding in vitro stability such
as prevention of denaturation or aggregation over the expected
shelf life. The selection of appropriate excipients also depends
upon the route of administration and the dosage form, as well as
the active ingredient and other factors.”
(Ans. 5 (footnote omitted).)
ANALYSIS
Based on the combination of STN and Yamazaki, Examiner concludes
that, at the time Appellant’s invention was made, it would have been prima
facie obvious to formulate the STN compound with a pharmaceutically
acceptable excipient (see Ans. 6–7). In this regard, Examiner reasons that a
person of ordinary skill in this art would have found that the STN compound
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Application 15/303,481

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is structurally similar to Yamazaki’s compound 35 and, thus, would consider
the STN “compound as a potential drug candidate just based on the structure
alone in combination with the teaching of Yamazaki showing a similar
compound having some activity in a virtual screen for PDE 1 and 5” (Ans. 6;
see id. (Examiner asserts that “one would view both these molecules as drug
like; having a molecular weight that is appropriate, a reasonable amount of
rings, and a reasonable amount of hetero-atoms”)).
According to Examiner, in an effort to learn more about the STN
compound, a person of ordinary skill in this art would have deconstructed
the STN compound into component parts, specifically a core, linker, and
aromatic group and then searched for closely related structures to these
components for combinations thereof (see Ans. 8–9). According to
Examiner, such a search would have led a person of ordinary skill in this art
to Yamazaki, which according to Examiner “bolsterers the opinion that a
POSITA would see this molecule as a drug-like compound” (Ans. 9).
We are not persuaded.
We appreciate that “[o]bviousness based on structural
similarity . . . can be proved by identification of some motivation that would
have led one of ordinary skill in the art to select and then modify a known
compound (i.e. a lead compound) in a particular way to achieve the claimed
compound.” Eisai Co. Ltd. v. Dr. Reddy’s Labs., Ltd., 533 F.3d 1353, 1357
(Fed. Cir. 2008). On this record, however, Examiner failed to establish an
evidentiary basis on this record to support a conclusion that Yamazaki
directs those of ordinary skill in this art to make the specific modifications to
its lead compounds that would have been necessary to arrive at the
compound set forth in STN or Appellant’s claims (see Appeal Br. 16
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(Appellant asserts that “[E]xaminer has not described how the cited
reference would have directed one to make the various modifications
necessary to convert Yamazaki[’s] compound 35 into . . . [the compound of
Appellant’s claimed invention])).
In addition, we agree with Appellant that “[e]ven supposing Yamazaki
screened a library of compounds containing [the compound of Appellant’s
claim] . . ., there is no evidence Yamazaki would have identified . . . [the
compound of Appellant’s claim] as useful in a pharmaceutical
formulation . . . for cardiovascular disease” (Appeal Br. 14). In this regard,
we note that Yamazaki discloses, at best, an expectation that its screening
method will identify a therapeutic for cardiovascular disease (FF 6).
STN’s disclosure does not aid this analysis. As Appellant explains,
the “database compound from STN does not describe [the compound of
Appellant’s claim as] . . . having any pharmaceutical use and Yamazaki does
not describe [the compound of Appellant’s claim as] . . . having any
pharmaceutical use,” thus, “it is not predictable based on compound 35 in
Yamazaki, that [the compound of Appellant’s claim] . . . would have a
specific pharmaceutical use” (Appeal Br. 15). In this regard, we remind
Examiner that an invention
composed of several elements is not proved obvious merely by
demonstrating that each of its elements was, independently,
known in the prior art. . . . [I]t can be important to identify a
reason that would have prompted a person of ordinary skill in
the relevant field to combine the elements in the way the
claimed new invention does.
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007). On this record,
Examiner failed to establish an evidentiary basis to support a conclusion of
obviousness. See In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006)
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(“[R]ejections on obviousness grounds cannot be sustained by mere
conclusory statements; instead, there must be some articulated reasoning
with some rational underpinning to support the legal conclusion of
obviousness.”).
CONCLUSION
The preponderance of evidence relied upon by Examiner fails to
support a conclusion of obviousness. The rejection of claims 7–9 under 35
U.S.C. § 103(a) as unpatentable over the combination of STN and Yamazaki
is reversed.
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
7–9 103 STN, Yamazaki 7–9

REVERSED