Ex Parte Sharma et al

Patent Trial and Appeal Board

Mar 4, 2015

12304007 (P.T.A.B. Mar. 4, 2015)

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.
12/304,007 12/09/2008 Shalini Sharma 18062-PCTUS 1537
31976 7590 03/04/2015
Wellstat Management Company. LLC
LEGAL DEPARTMENT
930 CLOPPER ROAD
GAITHERSBURG, MD 20878
EXAMINER
WEST, THEODORE R
ART UNIT PAPER NUMBER
1628
MAIL DATE DELIVERY MODE
03/04/2015 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte SHALINI SHARMA and REID W. VON BORSTEL
__________

Appeal 2012-008086
Application 12/304,007
Technology Center 1600
__________

Before JEFFREY N. FREDMAN, CHRISTOPHER G. PAULRAJ, and
ROBERT A. POLLOCK, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal
1
under 35 U.S.C. § 134 involving claims to
treatment method. The Examiner rejected the claims as obvious. We have
jurisdiction under 35 U.S.C. § 6(b). We affirm.

1
Appellants identify the Real Party in Interest as Wellstat
Therapeutics Corporation (see App. Br. 4).
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2
Statement of the Case
Background
“[D]iabetes remains a major and growing public health problem. Late
stage complications of diabetes consume a large proportion of national
health care resources. There is a need for new orally active therapeutic
agents which effectively address the primary defects of insulin resistance
and islet failure” (Spec. 2, ll. 10–14).
The Claims
Claims 3–10 are on appeal. Claim 3 is representative and reads as
follows:
3. A method for treating a mammalian subject with a
condition selected from the group consisting of insulin
resistance syndrome, diabetes, polycystic ovary syndrome,
hyperlipidemia, fatty liver disease, cachexia, obesity,
atherosclerosis and arteriosclerosis comprising
administering to the subject an amount of a biologically
active agent,
wherein the agent is selected from the group
consisting of: 3-(2,4-Bis(trifluoromethyl)benzyloxy)
phenylacetic acid; and its pharmaceutically acceptable salts.

The Issue
The Examiner rejected claims 3–10 under 35 U.S.C. § 103(a) as
obvious over Hodge
2
and Yale
3
(Ans. 4–6).

2
Hodge et al., WO 2004/073611 A2, published Sept. 2, 2004
(hereinafter “Hodge”).
3
Yale, H., The Trifluoromethyl Group in Medicinal Chemistry, 1 J.
MEDICINAL PHARMACEUTICAL CHEMISTRY 121–133 (1959).
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The Examiner finds that Hodge teaches 3-(2,6-dimethylbenzyloxy)
phenylacetic acid, which “is used in methods of treating insulin resistance
syndrome, diabetes, cachexia, hyperlipidemia, fatty liver disease, obesity,
atherosclerosis, and arteriosclerosis” (Ans. 4–5).
The Examiner acknowledges that “the prior art discloses 2,6-
substitution of the phenyl ring, whereas the pending claims are directed to
the positional isomer having 2,4-substitution of these methyl substituents,
which have been replaced by trifluoromethyl groups” (Ans. 5).
The Examiner finds that Yale teaches that “in the field of medicinal
chemistry, substitution of methyl groups for trifluoromethyl groups is
expected to produce new medicinal agents having similar properties as the
base structure but with the added benefit of physiological stability
attributable to the trifluoromethyl groups” (Ans. 5).
The Examiner finds it obvious to form the positional isomers and “to
substitute the methyl groups of the 2,4-dimethyl compound with
trifluoromethyl groups . . . because Hodge et al. specifically teaches that the
phenyl group may be substituted with such trifluoromethyl groups” (Ans. 6).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that Hodge and Yale render the claims
obvious?
Findings of Fact
1. The Specification teaches the following compound:

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The compound name is 3-(2,4-Bis(trifluoromethyl)benzyloxy)phenylacetic
acid (Spec. 10, ll. 1–6).
2. Hodge teaches a compound of Formula I:

where “A is phenyl, unsubstituted or substituted by 1 or 2 groups selected
from: halo, alkyl having 1 or 2 carbon atoms, perfluoromethyl
4
” (Hodge 3
(emphasis added)).
3. Hodge teaches the following compound:

The compound name is 3-(2,6-Dimethylbenzyloxy)phenylacetic acid (Hodge
34).
4. Hodge teaches
[A] method for treating a mammalian subject with a
condition selected from the group consisting of insulin
resistance syndrome and diabetes (both primary essential
diabetes such as Type I Diabetes or Type II Diabetes and

4
As noted by the Examiner, “perfluoromethyl” is synonymous
with “trifluoromethyl.” (See Ans. 6).
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secondary nonessential diabetes), comprising administering
to the subject an amount of a biologically active agent as
described herein effective to treat the condition. In
accordance with the method of this invention a symptom of
diabetes or the chance of developing a symptom of diabetes,
such as atherosclerosis, obesity, hypertension,
hyperlipidemia, fatty liver disease, nephropathy, neuropathy,
retinopathy, foot ulceration and cataracts, each such
symptom being associated with diabetes.

(Hodge 28.)
5. Hodge teaches that “[c]ompound CF was produced in
accordance with chemical synthesis example 1. . . . and Compound CF (60
mg/kg) elicited a significant reduction in blood glucose” (Hodge 59).
6. Yale teaches that:
[A] substantial effort has been devoted to the incorporation
of the trifluoromethyl group into such prototype molecules,
in some instances in place of a methyl group . . . . There are
a number of reasons for the selection of the trifluoromethyl
group for this purpose. First, it could be anticipated that the
new compounds and the prototypes would have similar
physical properties, and secondly, the new compounds
would be acceptable as medicinal agents in view of the
known unique chemical and physiological stability of the
trifluoromethyl group.

(Yale 121.)
7. Yale teaches that “a relatively large number of compounds
containing the trifluoromethyl group has been screened for pharmacological
and chemotherapeutic activity; that, of these, a number were found to be
sufficiently active to merit a trial in man; and, finally, from these latter
studies, have come a few useful pharmaceutical agents” (Yale 131).
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Principles of Law
In Dillon, the Federal Circuit noted:
In brief, the cases establish that if an examiner considers that
he has found prior art close enough to the claimed invention
to give one skilled in the relevant chemical art the
motivation to make close relatives (homologs, analogs,
isomers, etc.) of the prior art compound(s), then there arises
what has been called a presumption of obviousness or a
prima facie case of obviousness. [In re Henze, 181 F.2d 196
(CCPA 1950); In re Hass, 141 F.2d 122 (CCPA 1944)] The
burden then shifts to the applicant, who then can present
arguments and/or data to show that what appears to be
obvious, is not in fact that, when the invention is looked at
as a whole. . . . The cases of Hass and Henze established the
rule that, unless an applicant showed that the prior art
compound lacked the property or advantage asserted for the
claimed compound, the presumption of unpatentability was
not overcome.

In re Dillon, 919 F.2d 688, 696 (Fed. Cir. 1990).
Analysis
We adopt the Examiner’s findings of fact and reasoning regarding the
scope and content of the prior art (Ans. 4–9; FF 1–6) and agree that the
claims are rendered obvious by Hodge and Yale. We address Appellants’
arguments below.
Appellants contend that the “conclusion of obviousness is based, not
on the 2,6-dimethyl compound disclosed in Hodge in combination with
Yale, but rather on the hypothetical 2,4-dimethyl compound disclosed only
in the first step of the rejection’s analysis in combination with the supposed
teaching of Yale” (App. Br. 12).

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The Examiner responds that
[B]ridging the difference between the prior art and the
claims at issue in the present application requires a two-step
modification: first, moving the methyl groups from a 2,6-
substitution pattern to a 2,4-substition pattern, and second,
substituting the methyl groups for trifluoromethyl groups.
For each of these two steps, the rejection above provides a
statement of why one would be motivated to carry out the
step and why one would have had a reasonable expectation
of success.

(Ans. 7.)
We find that the Examiner has the better position. Hodge teaches a
generic formula where A is a phenyl group that may be substituted by 1 or 2
groups at any of the five available positions (FF 2). Hodge teaches that the
groups may be selected from a list of components including
perfluoromethyl, which is an alternative name for trifluoromethyl (FF 2).
Hodge teaches examples where the phenyl group at the A position is
substituted by two methyl groups at the 2 and 6 positions (FF 3). Finally,
Yale teaches that the trifluoromethyl group provides chemical and
physiological stability to compounds (FF 6).
We therefore agree with the Examiner that there would have been
reason to substitute the trifluoromethyl group for the methyl group, since
Hodge teaches that trifluoromethyl may be a substituent on the phenyl (FF
2) and since Yale teaches that trifluoromethyl has specific advantages of
stability (FF 6). We also agree with the Examiner that the further change to
the compound by ring walking one of the two trifluoromethyl substituents
suggested by Hodge and Yale from the 6 position exemplified in Hodge (FF
3) to the 4 position encompassed by the generic formula of Hodge (FF 2)
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creates a compound with sufficient structural similarity to reasonably shift
the burden to Appellants to demonstrate unexpected results for the claimed
compound, consistent with Dillon. Appellants have provided no rebuttal
evidence demonstrating the presence of any secondary consideration or
unexpected result based on either or both of the ring positions of the second
substituent or the selection of trifluoromethyl from the substituent list for the
A phenyl of Hodge.
Appellants also contend, based on Yale, that “[o]ut of a relatively
large number of compounds tested only a small number were useful. Thus
the person of ordinary skill in the art would not have had a reasonable
expectation that a given trifluoromethyl compound would have the same
biological activity as its methyl prototoype [sic]” (App. Br. 14).
We find this argument unpersuasive. Hodge demonstrates that the
compound of formula I results in significant reduction of blood glucose (FF
5). While Yale does state that there is some degree of unpredictability, Yale
also teaches that a “number of compounds” with the trifluoromethyl group
were “sufficiently active to merit a trial in man” (Yale 131; FF 7). We
conclude that the ordinary artisan would have found a reasonable
expectation of success in applying this combination in practical use. Kubin
stated that, “[r]esponding to concerns about uncertainty in the prior art
influencing the purported success of the claimed combination, this court [in
O’Farrell] stated: ‘[o]bviousness does not require absolute predictability of
success . . . all that is required is a reasonable expectation of success.”’ In
re Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009) (citing In re O’Farrell, 853
F.2d 894, 903–904 (Fed. Cir. 1988)). Here, the ordinary artisan with reason
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to select trifluoromethyl groups from the substituent list of Hodge for the
stability advantages identified by Yale, as well as ring walking the second
substituent as suggested by Hodge, would have a reasonable expectation of
success (FF 1–7).
Appellants cite Baird for the proposition that “the ‘fact that a claimed
compound may be encompassed by a disclosed generic formula does not by
itself render that compound obvious.’ In re Baird, 16 F.3d 380, 382, 29
USPQ2D 1550, 1552 (Fed. Cir. 1994)” (App. Br. 15).
We find this citation inapposite because Baird dealt with the situation
where “there is nothing in the disclosure [of the prior art] suggesting that one
should select such variables.” Baird, 16 F.3d at 382. In the instant case,
Hodge teaches that trifluoromethyl is a species in the genus of substituents
of the A phenyl group (FF 2) and Yale provides reasons to select
trifluoromethyl to replace methyl groups (FF 6–7). Therefore, unlike Baird,
there is specific disclosure in the prior art of Yale suggesting the selection of
trifluoromethyl groups to replace methyl groups.
Appellants contend that “if the Office’s methodology for evaluating
patentability were to be accepted, virtually any chemical compound could be
found obvious over any other chemical compound, no matter how different,
by invoking a sequence of small modifications each of which is thought to
be obvious in view of its immediate predecessor” (Reply Br. 2–3).
We find this argument unpersuasive because patentability does not
reside in the number of differences between a chemical compound and the
prior art but rather in the unobviousness of those differences. That is, when
the prior art provides reason to make a modification to a chemical
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compound, that modification may well be obvious, whereas when the prior
art provides no reason to make a modification, and the modification is not
simply an analog or homolog as in Dillon, the modification may be
unobvious. In the instant case, Hodge provides the generic suggestion of
ring positions in the phenyl group and the use of the trifluoromethyl as a
substituent (FF 2–3), while Yale provides a specific reason to substitute
trifluoromethyl groups in the place of a methyl group (FF 6–7). It is these
reasons which are outcome determinative, not the mere number of obvious
modifications.
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that
Hodge and Yale render the claims obvious.
SUMMARY
In summary, we affirm the rejection of claim 3 under 35 U.S.C.
§ 103(a) as obvious over Hodge and Yale. Pursuant to 37 C.F.R. § 41.37(c),
claims 4–10 fall with claim 3, as these claims were not argued separately.

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

AFFIRMED
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