Rigel Pharmaceuticals, Inc.

Patent Trials and Appeals Board

Mar 29, 2021

2020002152 (P.T.A.B. Mar. 29, 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.
15/677,809 08/15/2017 Simon Shaw 14-1845-US 6926
74839 7590 03/29/2021
Klarquist Sparkman, LLP
121 SW Salmon St
Suite 1600
Portland, OR 97204
EXAMINER
CHENG, KAREN
ART UNIT PAPER NUMBER
1626
NOTIFICATION DATE DELIVERY MODE
03/29/2021 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):
docketing@klarquist.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
_________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
_________________

Ex parte SIMON SHAW, XIANG XU, SARKIZ ISSAKANI, RAJINDER
SINGH, YASUMICHI HITOSHI, MATTHEW DUNCTON, and NAN LIN

_________________

Appeal 2020-002152
Application 15/677,809
Technology Center 1600
_________________

Before FRANCISCO C. PRATS, RAE LYNN P. GUEST, and
DEBORAH KATZ, Administrative Patent Judges.

KATZ, Administrative Patent Judge.

DECISION ON APPEAL
Appellant1 seeks our review2, under 35 U.S.C. § 134(a), of the
Examiner’s decision to reject claims 1–3, 5–9, and 27. We have jurisdiction
under 35 U.S.C. § 6(b). We AFFIRM.

1 We use the word “Appellant” as defined in 37 C.F.R. § 1.42. Appellant
identifies the real party in interest as Rigel Pharmaceuticals, Inc. (Appeal
Br. 2.)
2 We consider the Final Office Action issued April 19, 2019 (“Final Act.”),
the Appeal Brief filed September 13, 2019 (“Appeal Br.”), the Examiner’s
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Application 15/677,809

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The Examiner rejected Appellant’s claims under 35 U.S.C. § 103(a)
over Bookser (U.S. Patent 8,394,969 B2, issued March 12, 2013.) (See Final
Act. 5–8.) Appellant does not argue for the separate patentability of any of
the rejected claims. Accordingly, we focus on claim 1 in our review. See 37
C.F.R. § 41.37(c)(1)(iv).
Appellant’s Specification is directed to benzimidazole compounds,
which activate the 5’-AMP-activated protein kinase (“AMPK”) pathway and
can be used to treat diseases such as type II diabetes, atherosclerosis, and
cardiovascular disease. (Spec. ¶¶ 2, 5.)
Appellant’s claim 1 recites a compound having the structure of
formula (I), wherein formula (I) is depicted as:

or a pharmaceutically acceptable salt, prodrug or N-oxide thereof, or solvate
or hydrate thereof, wherein R1–R4, X, and Y can be many different, recited
substructures. (See Appeal Br. 9–13.) Claim 1 includes a list of species not
included in the scope of the recited genus. (See id. 10–14.)
Bookser teaches compounds that are AMPK activators useful in the
treatment of type II diabetes, hyperglycemia, metabolic syndrome, obesity,
hypercholesterolemia, and hypertension. (See Bookser abstract.) The

Answer issued on November 20, 2019 (“Ans.”), the Reply Brief filed
January 21, 2020 (“Reply Br.”).
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Examiner finds Bookser to teach that only the benzimidazole core is
essential to the activity of the compounds it discloses. (See Ans. 10.)
Appellant does not dispute this finding.
The Examiner cites to two specific compounds taught in Bookser.
First, the Examiner finds that Bookser teaches the compound of Example 33,
which has the general formula:

(See Final Act. 5, citing Bookser cols. 101–102, Example 33.) The
Examiner finds that this compound is the same as a compound within the
scope of formula (I) in Appellant’s claim 1, wherein
R1 is Ar, R2 is H, R3 as chloro, X is O, R4 is C1-6alkyl, Y is ,
and RY is H. (See Final Act. 5.) The Examiner acknowledges that this
specific compound is expressly excluded from Appellant’s claim 1. (See id.)
The Examiner finds, though, that one of ordinary skill would have
considered it obvious to substitute the hydrogen provided for RY in Bookser
for a methyl group to arrive at a compound encompassed by Appellant’s
claim 1. (See Final Act. 5–6.) The Examiner finds that the substitution of a
methyl group for a hydrogen atom would have been obvious to those of
ordinary skill in the art citing to the teaching in Bookser that substituent
groups such as hydrogen, halogens, and C1–6 alkyl can be substituted for
each other, as well as substitutions of C1–6 alkyl for phenyl. (See Final Act.
6, citing Bookser 6:39–42.) The Examiner cites further to In re Wood, 582
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F.2d 638 (CCPA 1978), which holds that the difference between hydrogen
and alkyl substituent groups would have been obvious to those of ordinary
skill in the art because of the close structural similarity between the claimed
compounds and the prior art.
The Examiner also finds that Bookser teaches the following
compound in Example 53:

(See Final Act. 5, citing Bookser cols. 109–110, Example 53.) The
Examiner finds that the compound of Example 53 corresponds to a
compound of formula (I) of Appellant’s claim 1, specifically that it is a
positional isomer of a compound recited in Appellant’s claim 9. (See Final
Act. 7.)
Bookser is directed to compounds that are activators of AMPK
activity. (See Bookser abstract.) Bookser demonstrates it has achieved this
goal with the statement:
The compounds of Examples 1-365 were tested in the in vitro
AMPK activation assay using recombinant human AMPK complex 1
(containing α1β1γ1) and found to have EC50 values of less than 10
micromolar and greater than 80% maximum AMP activation.
(See Bookser col. 258, ll. 60–64.) Thus, all of the compounds, including
those of Examples 33 and 53, are disclosed as having effective level of
AMPK activation activity in an in vitro assay.
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Appellant does not dispute the differences between the compounds of
Bookser identified by the Examiner or that the modified compounds would
fall within the scope of claim 1. Nor does Appellant dispute the Examiner’s
finding that Bookser teaches only the benzimidazole core is essential to the
activity of the compounds it discloses. (See Ans. 10.)
Appellant argues, instead, that there is no basis in the prior art for
selecting the compounds of Example 33 or 53 of Bookser because there is
nothing that would distinguish them from the other 363 compounds
disclosed in Bookser. (See Appeal Br. 7; see Reply Br. 3–4.) Appellant
argues that the Examiner fails to identify an attractive characteristic of the
two compounds noted and that Bookser fails to report any biological activity
for these compounds. (See Appeal Br. 7; see Reply Br. 4.) Appellant cites
to Daiichi Sankyo Co., Ltd. v. Matrix Labs. Ltd., 619 F.3d 1346, 1354 (Fed.
Cir. 2010), arguing that a lead compound must be identified in the prior art.
Appellant argues that “‘proving a reason to select a compound as a lead
compound depends on more than just structural similarity, but also
knowledge in the art of the functional properties and limitations of the prior
art compounds. Potent and promising activity in the prior art trumps mere
structural relationships.’” (Appeal Br. 7, quoting Daiichi, 619 F.3d at 1354.)
According to Appellant, without the identification of attractive properties of
the two compounds cited by Bookser, the Examiner must have relied on
hindsight to reject Appellant’s claims. (See Appeal Br. 7–8.)
We are not persuaded by Appellant’s argument. At the outset, we
note that Appellant mischaracterizes Bookser because Bookser teaches
biological activity for the two compounds highlighted by the Examiner.
Bookser teaches that “[t]he compounds of Examples 1-365 were tested in the
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in vitro AMPK activation assay . . . and found to have EC50 values of less
than 10 micromolar and greater than 80% maximum AMP activation.”
(Bookser col. 258, ll. 60–64.) Thus, Bookser teaches that the compounds of
Examples 33 and 53, like all of the compounds disclosed, have significant
biological activity. We note that Appellant’s Specification also provides an
in vitro assay as the only evaluation of biological activity of the claimed
compounds. (See Spec. ¶ 211 (“representative compounds activate AMPK
with an EC50 of less than 20 micromolar, less than 10 micromolar or less
than 1 micromolar”).)
Furthermore, we are also not persuaded that the Examiner must have
identified a single lead compound in Bookser to demonstrate that the
claimed compounds would have been obvious. The Daiichi court noted that
[w]hile the lead compound analysis must, in keeping with KSR, not
rigidly focus on the selection of a single, best lead compound . . . the
analysis still requires the challenger to demonstrate by clear and
convincing evidence that one of ordinary skill in the art would have
had a reason to select a proposed lead compound or compounds over
other compounds in the prior art.
Daiichi, 619 F.3d at 1354. Because the compounds of Examples 33 and 53
were shown to have AMPK activation activity in in vitro assays, as
Appellant’s claimed compounds, we are persuaded that there would have
been a reason to select them. We are not persuaded that the same activity of
other compounds disclosed in Bookser negates the reasons why one of
ordinary skill would have modified the compounds of Examples 33 and 53.
Appellant does not dispute the reasons the Examiner provides for why
one of ordinary skill would have considered the modifications of the
compounds of Bookser to achieve a compound within the scope of
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Appellant’s claims. Nor does Appellant direct us to evidence of increased
efficacy of the claimed compounds over those taught in Bookser or to any
other unexpected results that should be considered in a determination of
obviousness. Accordingly, we are not persuaded that Appellant’s claimed
compounds would have been unobvious over the compounds taught in
Bookser.
Conclusion
Upon consideration of the record and for the reasons given, we affirm
the Examiner’s rejection.
In summary:
Claim(s)
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1–3, 5–9, 27 103(a) Bookser 1–3, 5–9, 27

No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1)(iv).

AFFIRMED