Ex Parte Foricher et al

Patent Trial and Appeal Board

Jul 8, 2014

12647056 (P.T.A.B. Jul. 8, 2014)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte YANN FORICHER, MARTIN SMRCINA,
VIVIANE VAN DORSSELAER, and FABIENNE WEBER
__________

Appeal 2012-004073
Application 12/647,056
Technology Center 1600
__________

Before DEMETRA J. MILLS, ERIC B. GRIMES, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving claims to
derivatives of pyrazole 3,4-carboxylates. The Examiner rejected the claims
as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We reverse.

1 Appellants identify the Real Party in Interest as Sanofi-Aventis
(see App. Br. 2).
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Statement of the Case
Background
The Specification teaches “derivatives of pyrazole 3,5-carboxylates,
their preparation and their applications in therapeutics” (Spec. 1, ll. 9-10).
The Specification also teaches that “these compounds, derived from
pyrazole 3,5-carboxylates, are inhibitors of β-secretase BACE1 (β-site
amyloid precursor protein cleavage enzyme subtype 1)” (Spec. 1, ll. 12-14).
The Claims
Claims 1-3, 5, 7, 8, 10, and 11 are on appeal. Claim 1 is the only
independent claim and is directed to a compound of the following formula
(I):

in which n, R1 through R5, Q, V, W, X, and Y are further defined. The full
text of claim 1 is reproduced in the Claims Appendix of the Appeal Brief.

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The issue2
The Examiner rejected claims 1-3, 5, 7, 8, 10, and 11 under 35 U.S.C.
§ 103(a) as obvious over WO 2003/040096 A2 (hereinafter WO ’096) (Ans.
7).
The Examiner finds that WO ’096 teaches compound Ex 3125
reproduced below:

(Ans. 7). The Examiner finds that the “WO [’]096 publication also teaches
and discloses that the compound[s] are inhibitors of beta-secretase and that
the class of compound[s] are useful in treating Alzheimer’s disease (AD)
and similar diseases” (id. at 8). The Examiner finds that the “difference
between the compounds of the instant claim 1 and the compounds in the WO
‘096 publication is that the -N- on the pyrazole ring is unsubstituted in
disclosed species in the WO ‘096 publication, while R3 in instant Formula
(I) may represent a lower alkyl (i.e., methyl)” (id.). That is, the disclosed
compound includes a pyrazole ring having the structure but the
claims on appeal require at least a methyl group where the disclosed
compound has an –NH group. The Examiner concludes that the “structural

2 We note that claims 4 and 9 were objected to, but not rejected.
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modification of the pyrazole ring would have been prima facie obvious in
view of the suggestion of such modification in the prior art itself” (id. at 9).
Appellants contend that “[n]o prima facie case of obviousness exists
under the appropriate standard of assessment; and no motivation on any
objective basis exists to make the selections and modifications officially
alleged” (App. Br. 4). Appellants further contend that “without benefit of
the instant specification and claims, one cannot, and would not be able to
credibly say that the artisan would chose Formula Z1 over Formula Z2, and
then look to Examples 1347, 3660, 3743 and, finally, 3125, from all the
other enormous number of compounds, for purposes of selecting a route to
modify WO ‘096” (App. Br. 10). Appellants also contend that the long
“recitation of R30 possibilities that proceeds for some number of pages, that
the so-called ‘finite number of options’” provide “no objectively sound
reason to make this choice that is derivable from the reference itself” (id. at
11).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that the claimed compounds are obvious
over the cited prior art?
Findings of Fact
The following findings of fact (“FF”) are supported by a
preponderance of the evidence of record.
1. The Specification teaches that the compounds for formula I “are
inhibitors of β-secretase BACE1 (β-site amyloid precursor protein cleavage
enzyme subtype 1)” (Spec. 1, ll. 12-14).
2. Claim 1 includes compounds of formula I where R3 may
represent a lower alkyl (see Claim 1).
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3. WO ’096 teaches that the compounds are inhibitors of beta-
secretase, which is useful for treating Alzheimer’s disease (see Ans. 8).
4. WO ’096 teaches compound 3125 as reproduced below:

The chemical name of compound 3125 is N5-{(1S,2R)-1-(3, 5-
difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-N3, N3 -
dipropyl-1H-pyrazole-3,5-dicarboxamide.
5. Compound 3125 in WO ’096 differs from Appellants’ formula I
because both nitrogen atoms on the pyrazole ring are unsubstituted while
Appellants’ formula I requires an R3 substituent on one of the nitrogens,
where R3 may represent a lower alkyl (see FF 2; Ans. 8).
6. WO ’096 teaches compounds where an alkyl may be substituted
for the unsubstituted pyrazolyl ring (see WO ’096 279, 878, 899; compounds
1347, 3660, and 3752; Ans. 14).
7. WO ’096 discloses 3980 example species as well as other
variants (see App. Br. 3).
8. WO ’096 discloses eight biological examples, but each of these
examples is written in the present tense (see WO ’096 850-858), suggesting
that the examples were prophetic and not performed prior to filing. See
Atlas Powder Co. v. E.I. du Pont De Nemours & Co., 750 F.2d 1569, 1578
(Fed. Cir. 1984) (“the examples were written in the present tense to conform
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with the PTO requirements on prophetic examples.”) The examples do not
show any results for any specific compound, including compound 3125 (see
WO ’096 850-858).
Principles of Law
The test for prima facie obviousness in new chemical compounds is a
two part inquiry. Otsuka Pharm. Co., Ltd. v. Sandoz, Inc., 678 F.3d 1280,
1291 (Fed. Cir. 2012). The first part is “whether a chemist of ordinary skill
would have selected the asserted prior art compounds as lead compounds, or
starting points, for further development efforts.” Id. The second part 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 lead compound is defined as “‘a compound in the prior art that
would be most promising to modify in order to improve upon its ... activity
and obtain a compound with better activity.’” Id. at 1291 (citing Takeda
Chem. Indus., Ltd. v. Alphapharm Pty., Ltd., 492 F.3d 1350, 1357 (Fed. Cir.
2007)). Stated another way, “a lead compound is ‘a natural choice for
further development efforts.’” Id. (citing Altana Pharma AG v. Teva Pharm.
USA, Inc., 566 F.3d 999, 1008 (Fed. Cir. 2009)). The lead compound
determination “must, in keeping with KSR, not rigidly focus on the selection
of a single, best lead compound.” Daiichi Sankyo Co., Ltd. v. Matrix
Laboratories, Ltd., 619 F.3d 1346, 1354 (Fed. Cir. 2010). The analysis of
whether a chemist of ordinary skill would have chosen the prior art
compound as a lead compound “is guided by evidence of the compound’s
pertinent properties” including “positive attributes such as activity and
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potency,” “adverse effects such as toxicity,” “and other relevant
characteristics in evidence.” Otsuka, 678 F.3d at 1292.
Importantly, “[a]bsent a reason or motivation based on such prior art
evidence, mere structural similarity between a prior art compound and the
claimed compound does not inform the lead compound selection.” Id.; see
also Daiichi, 619 F.3d at 1354 (“[P]roving 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.”).
Analysis
Appellants contend that the Examiner improperly selected compound
3125 of WO ’096 as the lead compound (App. Br. 4). Appellants contend
that skilled artisans would not have “vetted through this mammoth
disclosure, and … objectively chosen, from among the enormous number
and diverse teachings of WO ‘096, very select compounds, and then would
have modified same in such specific ways as to make the appealed
compound, as defined in Claim 1, legally obvious” (App. Br. 4).
We agree with Appellants that the Examiner has not shown that a
skilled artisan would have had a reason to select compound 3125 as the lead
compound. In particular, the Examiner has not established that WO ’096
teaches that compound 3125 has any particular functional activity which
suggests compound 3125 should serve as a lead compound. As stated in
Otsuka, structural similarities alone are not enough to inform the lead
compound selection. In fact, the Examiner does not establish that there is
any data for any of the specific compounds in WO ’096. Therefore, the
Examiner has not provided sufficient reason to show that it would been
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obvious to select any specific one of the compounds from the thousands of
different compounds disclosed in WO ’096. Under Daiichi it is possible to
have multiple lead compounds, but due to the large number of compounds
disclosed in WO ’096, it would not be reasonable to classify all 3980
exemplified compounds as joint lead compounds. We are therefore
persuaded by Appellants that the Examiner has not shown that a skilled
artisan would have been led to treat compound 3125 as a lead compound that
would have been obvious to modify.
We do agree with the Examiner that the modification to the pyrazole
ring would have been an obvious modification, had there been adequate
reason to select compound 3125 as the lead compound. However, the
Examiner has failed to make a prima facie case of obviousness because there
was no good reason given to select compound 3125 as the lead compound.

SUMMARY
In summary, we reverse the rejection of claims 1-3, 5, 7, 8, 10, and 11
under 35 U.S.C. § 103(a) as obvious over WO ’096.

REVERSED

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