VERTEX PHARMACEUTICALS INCORPORATED

Patent Trials and Appeals Board

May 12, 2021

2020006744 (P.T.A.B. May. 12, 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.
14/906,089 01/19/2016 Sara Sabina HADIDA-RUAH 67573-303561 6070
102256 7590 05/12/2021
Barnes & Thornburg, LLP (Vertex)
4208 Six Forks Road, Suite 1010
Raleigh, NC 27609
EXAMINER
CHONG, YONG SOO
ART UNIT PAPER NUMBER
1627
NOTIFICATION DATE DELIVERY MODE
05/12/2021 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):
docket-RA@btlaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte SARA SABINA HADIDA-RUAH, COREY ANDERSON,
ANDREAS P. TERMIN, BRIAN RICHARD BEAR,
VIJAYALASMI ARUMUGAM, PAUL KRENITSKY, and
JAMES PHILIP JOHNSON
__________

Appeal 2020-006744
Application 14/906,089
Technology Center 1600
__________

Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and
TAWEN CHANG, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1,2 under 35 U.S.C. § 134 involving claims to
compounds of Formula I. The Examiner rejected the claims as obvious. 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 Vertex
Pharmaceuticals Incorporated (see Appeal Br. 3).
2 We have considered and refer to the Specification of Jan. 19, 2016
(“Spec.”); Final Office Action of June 18, 2019 (“Final Action”); Appeal
Brief of May 18, 2020 (“Appeal Br.”); and Examiner’s Answer of July 29,
2020 (“Ans.”). An oral hearing was held on May 6, 2021.
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Statement of the Case
Background
“[T]here are many conditions where pain persists beyond its
usefulness, or where patients would benefit from inhibition of pain” (Spec.
¶ 2). “Voltage-gated sodium channels (Nav’s) play a critical role in pain
signaling” (id. ¶ 3). “Nav channels have long been considered likely targets
to reduce pain in conditions where hyperexcitability is observed” (id.).
“[U]pon their discovery, Nav1.8 channels were identified as likely targets for
analgesia . . . Nav1.8 is essential for spontaneous firing in damaged neurons,
like those that drive neuropathic pain” (id. ¶ 5). “Since Nav1.8 is primarily
restricted to the neurons that sense pain, selective Nav1.8 blockers are
unlikely to induce the adverse events common to non-selective Nav
blockers” (id. ¶ 6).
“Accordingly, there remains a need to develop additional Nav channel
antagonists preferably those that are more Nav1.8 selective and more potent
with increased metabolic stability and with fewer side effects” (Spec. ¶ 6).
The Claims
Claims 1–3, 12, 13, 16, 17, 20, 21, 32, 37, and 38 are on appeal. The
Examiner required a species election on June 5, 2017. The Examiner does
not appear to have extended the search to the entire genus. We therefore
limit our consideration of the merits of the appealed rejection to the elected
species. See Ex parte Ohsaka, 2 USPQ2d 1460, 1461 (BPAI 1987). Thus,
we focus on the elected 2-(4-fluorophenoxy)-N-(3-sulfamoylphenyl)-4-
(trifluoromethyl) benzamide chosen by Appellant in the Response filed June
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5, 2017. We reproduce claim 1 and partially reproduce claim 20 to show the
elected species as follows:
1. A compound of formula I:

or a pharmaceutically acceptable salt thereof,
wherein, independently for each occurrence:
R1 is H, Cl, CH3, CF3 or cyclopropyl;
R2 is H, F, Cl, CN, CH3, CF3 or CHF2;
R3 is H, F, Cl, CN, CF3, OCF3 or CF2CF3;
R4 is H;
R5 is H, F, Cl, CH3, OCH3, OCH2CH3, OCH2CH2CH3 or OCHF2;
R5’ is H, F, Cl, CH3, OCH3, OCH2CH3, OCH2CH2CH3 or OCHF2;
R6 is H, F or Cl;
R6’ is H, F or Cl; and
R7 is H, F, Cl, OCH3, OCF3, OCH2CH3, OCH(CH3)2 or OCHF2;

provided that R1, R2, and R3 are not simultaneously hydrogen; and
that R5, R5’, R6, R6’, and R7 are not simultaneously hydrogen.

20. The compound or salt of claim 1, wherein the compound or a
pharmaceutically acceptable salt thereof, is selected from the group
consisting of:
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2-(4-fluorophenoxy)-N-(3-sulfamoylphenyl)-4-(trifluoromethyl)
benzamide . . . .

Appeal Br. 20, 22–23.

The Rejection
The Examiner rejected claims 1–3, 12, 13, 16, 17, 20, 21, 32, 37, and
38 under 35 U.S.C. § 103(a) as obvious over Joshi3 (Ans. 3–4).
The Examiner finds the claims “are directed to the compound of
formula I, 2-(4-fluorophenoxy)-N-(3-sulfamoylphenyl)-4-
(trifluoromethyl)benzamide” (Final Act. 3). The Examiner finds Joshi
teaches a “preferred compound is of general formula Ill-A, wherein R3 is Q-
RX, wherein Q is C1 and RX is halogen (claim 53). A preferred R3 moiety at
this position is trifluoromethyl” (id.). The Examiner finds Joshi also teaches
compound 78 (id.).
The Examiner acknowledges Joshi fails “to disclose the
trifluoromethyl moiety of compound 78” (Final Act. 3). The Examiner finds
it obvious “to substitute the tert-butyl moiety with a trifluoromethyl moiety
for compound 78 because Joshi et al. teaches that the R3 moiety can be a C1
alkyl substituted with a halogen, in general, and specifically a trifluromethyl

3 Joshi et al., US 2007/0238733 A1, published Oct. 11, 2007.
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moiety” with a reasonable expectation of success (id.).
The issue with respect to this rejection is: Does a preponderance of
the evidence of record support the Examiner’s conclusion that the elected
species would have been obvious over the disclosure of Joshi?
Findings of Fact
1. Joshi teaches “compounds useful as inhibitors of voltage-gated
sodium channels. The invention also provides pharmaceutically acceptable
compositions comprising the compounds of the invention and methods of
using the compositions in the treatment of various disorders” (Joshi ¶ 2).
2. Joshi teaches, in Table 1, compound 78 reproduced below:

Compound 78 is 2-(4-fluorophenoxy)-4-tert-butyl-N-(3-aminosulfonyl)
phenyl)benzamide (Joshi 27, Table 1).
3. Joshi teaches “[i]n certain embodiments for compounds of
formula III-A, R3 is selected from halogen” and “each R5 is independently
selected from CN, CF3” (Joshi ¶¶ 156, 164, 169).
Principles of Law
Under the lead compound analysis rubric, we must first “determine[]
whether a chemist of ordinary skill would have selected the asserted prior art
compounds as lead compounds, or starting points, for further development
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efforts.” Otsuka Pharm. Co. v. Sandoz, Inc., 678 F.3d 1280, 1291 (Fed. Cir.
2012). “The second inquiry in the analysis is whether the prior art would
have supplied one of ordinary skill in the art with a reason or motivation to
modify a lead compound to make the claimed compound with a reasonable
expectation of success.” Id. at 1292.
A prima facie case for obviousness requires “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).
Analysis
Appellant contends
the Examiner has not provided a reason or rationale why the
skilled artisan would start with compound 78 of Joshi and make
specific selections necessary to modify the compound and
arrive at Appellant’s invention with a reasonable expectation of
success. Because the Examiner did not carry out a lead
compound analysis, as required by Federal Circuit precedent,
Appellant provides below a detailed analysis based on accepted
lead compound analysis which shows that the rejection fails to
demonstrate that the claimed compounds are prima facie
obvious over Joshi.
(Appeal Br. 7–8). Appellant contends “the Examiner has not demonstrated
that a person of ordinary skill would have selected compound 78 of Joshi as
a lead compound for further development efforts.” (Id. at 8). Appellant
contends “a person of ordinary skill selecting a compound from Joshi for
further development would have had no reason to select compound 78 as a
lead compound over one of the compounds for which activity data are
provided” (id. at 9). Appellant further contends “the Examiner does not
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articulate a reason for modifying the alleged lead compound (i.e., compound
78 of Joshi) to replace the tert-butyl group of compound 78 (at the position
corresponding to R3 of formula III-A) with a CF3 group based on some
specific disclosure therein” (id. at 10). Appellant points out that “none of
the disclosed species falling within formula III-A has a CF3 group at the R3
position” (id. at 12).
The Examiner finds “the mere fact that Joshi provides or doesn’t
provide NaV 1.8 channel inhibition values for compound 78 matters little,
since it is well-settled that disclosed examples and preferred embodiments
do not constitute a teaching away from a broader disclosure or nonpreferred
embodiments” (Ans. 5). The Examiner also finds “the question is not
whether it is obvious to modify the tert-butyl group with CF3, since CF3 is
already taught to be a moiety within limited choices taught by Joshi at that
particular position” (id. at 6).
We agree with Appellant. Whether in the context of a lead compound
analysis or in selecting known equivalents, the burden is on the Examiner to
establish a prima facie case. The Examiner has not done so.
If we apply the lead compound analysis, the Examiner does not
identify a specific compound as the lead compound and does not provide
any reason to select compound 78 of Joshi as the lead compound for the
reasons given by Appellant. To the extent that a compound in Joshi might
be selected as the lead compound, one of the five compounds with less than
2 µM activity in Table 3 (marked A), compounds 1, 7, 16, 21, and 23 would
be the most reasonable choices (see Joshi ¶ 299). However, the Examiner
does not analyze these compounds.
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Alternatively, if we apply the obvious equivalents/overlapping genus
analysis of the Examiner, the Examiner does not establish that the selections
made in the rejection were obvious equivalents. The disclosure of a genus
does not necessarily implicitly describe every subgenus encompassed by that
genus. In re Smith, 458 F.2d 1389, 1395 (CCPA 1972). Ruschig explained
this standard by analogizing a genus and its constituent species to a forest
and its trees, noting that,
It is an old custom in the woods to mark trails by making blaze
marks on the trees. It is no help in finding a trail . . . to be
confronted simply by a large number of unmarked trees.
Appellants are pointing to trees. We are looking for blaze marks
which single out particular trees. We see none.
In re Ruschig, 379 F.2d 990, 994–95 (CCPA 1967). Here, the Examiner has
not provided any blaze marks directing the ordinary artisan to select the
elected species. There is no persuasive reason given in the rejection to select
the particular substituents necessary to obtain the elected species.
Conclusion of Law
A preponderance of the evidence of record support the Examiner’s
conclusion that the elected species would have been obvious over the
disclosure of Joshi.
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DECISION SUMMARY
In summary:
Claim(s)
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1–3, 12, 13,
16, 17, 20, 21,
32, 37, 38
103 Joshi 1–3, 12,
13, 16, 17,
20, 21, 32,
37, 38

REVERSED