Ex Parte Moinet et al

Board of Patent Appeals and Interferences

Jul 26, 2010

10497491 (B.P.A.I. Jul. 26, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte GERARD MOINET, DOMINIQUE MARAIS,
and PHILIPPE MAIZERAY
__________

Appeal 2010-000898
Application 10/497,491
Technology Center 1600
__________

Before CAROL A. SPIEGEL, TONI R. SCHEINER, and STEPHEN
WALSH, Administrative Patent Judges.

WALSH, Administrative Patent Judge.

DECISION ON APPEAL1
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method for treating inflammation. The Patent Examiner rejected the claims
on the ground of obviousness. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing,
as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE”
(paper delivery mode) or the “NOTIFICATION DATE” (electronic delivery
mode) shown on the PTOL-90A cover letter attached to this decision.
Appeal 2010-000898
Application 10/497,491

2
STATEMENT OF THE CASE
The invention “relates to the use of a 4-oxobutanoic acid derivative
for the preparation of a pharmaceutical composition for treating
inflammation.” (Spec. 1, ll. 3-5.) “The inflammation treated according to
the invention may be associated with pathologies of insulin-resistant
metabolic syndrome, with pathologies resulting from diabetes, for instance
retinopathy, nephropathy, neuropathy, micro- and macro-angiopathy,
hypertension or atherosclerosis.” (Id. at 3, ll. 29-32.)
Claims 2, 3, 10, 11, 13, 15, 17-19, 22 and 23 are on appeal.2 Claim 2
is representative; the full text appears in the Claims Appendix. (App. Br. 9.)
Claim 2 lists several kinds of inflammation to be treated, and lists several
compounds that may be used. At the start of examination, the Examiner
required Appellants to elect a type of inflammation and a species of
compound, “to which the claims shall be restricted if no generic claim is
finally held to be allowable.” (Office action, July 17, 2007, page 4.)
Appellants elected diabetic neuropathy and 2-benzyl-4-(4-fluorophenyl)-4-
oxobutanoic acid. (Response, July 31, 2007, page 7.) Editing claim 2 to
focus on the subject matter elected for examination yields a shortened
version of the claim:
2. A method for treating inflammation, which inflammation
is diabetic neuropathy . . . comprising administering to a subject
in need thereof an effective amount of . . . 2-benzyl-4-(4-
fluorophenyl)-4-oxobutanoic acid . . . or a salt thereof.

2 According to Appellants’ Brief, claims 1, 4-9, 12, 16, 20 and 21 were
cancelled, and claim 14 was withdrawn from consideration. (App. Br. 1-2.)
Appeal 2010-000898
Application 10/497,491

3
The Examiner rejected claims 2, 3, 10, 11, 13, 15, 17-19, 22
and 233 under 35 U.S.C. § 103(a) as unpatentable over Pharmacia &
Upjohn S.O.A. (WO 97/17317)4 and Lal5. (Final Rej. 2.)

OBVIOUSNESS
The Issue
The Examiner’s position is that Pharmacia taught treating
inflammation with 4-phenyl-4-oxo-butanoic acid derivatives. (Ans. 3.)
According to the Examiner, it would have been obvious to pick and choose
various substituents from Pharmacia’s general formula of claim 1, “given the
teaching that the class of compounds has similar kynurenine-3-hydoxyase
[sic] inhibiting activity.” (Id.) Pharmacia disclosed compounds such as 2-
benzyl-4-(3’,4’-dichlorophenyl)-4-oxo-butanoic acid, having two halogens
(chlorine), in contrast to Appellants’ elected compound which has one atom
of fluorine. (Id.) The Examiner found that “replacing two halogens for a
different halogen would be expected to have the same activity,” and that the
elected species therefore would have been obvious. (Id. at 4.) In the
absence of an allegation of an unexpected result, the Examiner concluded
that any kynurenine hydroxylase inhibitor within Pharmacia’s generic
formula, including Appellants’ elected species, would have been obvious.

3 We list the claims rejected in the Final Rejection. The Examiner’s Answer
has apparent typos adding claims 20 and 21 and omitting claim 23. (Ans. 3.)
Appellants’ Brief tracks the claims listed in the Final Rejection (App. Br. 2),
and the Answer’s “Status of Claims” agrees with Appellants’ statement
(Ans. 2).
4 WO 97/17317, filed by Pharmacia & Upjohn S.O.A., published May 15,
1997.
5 US 6,060,250, issued to Preeti Lal et al., May 9, 2000.
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4
The Examiner found that although “Pharmacia … does not relate
inflammations of the brain to diabetic neuropathy,” Lal taught treating
diabetic neuropathy by inhibiting the kynurenine metabolic pathway, and it
would have been obvious to use a Pharmacia compound, modified as the
Examiner suggested, in Lal’s treatment method. (Id.)
Appellants contend that the rejection did not provide a reason “why
one of ordinary skill in the art would have picked the allegedly closest
compound to the claimed invention as the lead compound as a candidate for
modifications.” (App. Br. 5.) Appellants further contend that there was no
specific guidance to convert Pharmacia’s benzyl-4-(3’,4’-dichlorophenyl)-4-
oxo-butanoic acid to Appellants’ 2-benzyl-4-(4-fluorophenyl)-4-oxobutanoic
acid. (Id. at 8.) Appellants argue that Lal does not support the Examiner’s
conclusions. (Reply 4-5.) Specifically, Appellants dispute that Lal taught
inhibiting the kynurenine pathway with compounds like Pharmacia’s. (Id.)
According to Appellants, Lal instead taught administering HUTRAN, or a
derivative thereof, to treat neurological disorders. (Id. at 5, quoting Lal, col.
20, ll. 49-53.)
The issues with respect to this rejection are:
whether there was a reason to select benzyl-4-(3’,4’-dichlorophenyl)-
4-oxo-butanoic acid from the compounds in Pharmacia’s claim 10;
whether there was a reason to convert the compound selected from
Pharmacia’s claim 10 to 2-benzyl-4-(4-fluorophenyl)-4-oxobutanoic acid;
and
whether the evidence supports the Examiner’s findings concerning the
content of the Lal disclosure.

Appeal 2010-000898
Application 10/497,491

5
Findings of Fact
1. Pharmacia taught 4-phenyl-4-oxo-butanoic acid derivatives for use as
kynurenine-3-hydroxylase inhibitors in the prevention and treatment
of neurodegenerative disease. (Pharmacia, Abstract.)
2. Pharmacia disclosed generic formula (I) in which hydrogen and
halogen were potential substituents, among others. (Id., claim 1.)
3. Pharmacia claimed the compound benzyl-4-(3’,4’-dichlorophenyl)-4-
oxo-butanoic acid, among others. (Id., claim 10.)
4. The Examiner found that
it would be obvious to substitute[] halogens, i.e. fluorine for a
chlorine, as substituent Y. These substitutions would have been
obvious to one of ordinary skill in the art because the halogens
are not reactive and simply stabilize the aromatic ring.
Therefore, replacing two halogens for a different halogen would
be expected to have the same activity.

(Ans. 3-4.)
5. The Examiner found that Lal taught that “inhibition of kynurenine
metabolic pathway stops the conversion of kynurenine to kynurenic
acid, which is an antagonist of the N-methyl-D-asparta[t]e (NMDA)
receptor in the brain.” (Ans. 4.)
6. The Examiner found that Lal disclosed using compounds that stop the
conversion of kynurenine to kynurenic acid to treat diabetic
neuropathy. (Id.)
7. In the “Background of the Invention,” Lal disclosed that the enzyme
glutamine-phenylpyruvate aminotransferase, aka glutamine
transaminase (GTK) catalyzes the conversion of kynurenine to
kynurenic acid, and that “[k]ynurenic acid . . . is an antagonist of the
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6
N-methyl-D-aspartate (NMDA) receptor in the brain and may exert a
neuromodulatory function.” (Lal, col. 1, ll. 22-32.)
8. In the “Background of the Invention,” Lal disclosed that “the enzyme
kynurenine/α-aminoadipate aminotransferase (AadAT) catalyzes …
the reversible conversion of α-aminoadipate and α-ketoglutarate to α-
ketoadipate and L-glutamate. . . . AadAT also catalyzes the
transamination of kynurenine acid to kynurenic acid.” (Id. at col. 1, ll.
50-56.)
9. Lal stated that its invention “features substantially purified
polypeptides, human transferases, referred to collectively as
‘HUTRAN’ and individually as ‘HUTRAN-1’, ‘HUTRAN-2’, and
‘HUTRAN-3.’” (Id. at col. 2, ll. 40-44.)
9. Lal taught that “HUTRAN or a fragment or derivative thereof may be
administered to a subject to treat or prevent a neurological disorder.”
(Id. at col. 20, ll. 33-35.)
10. Diabetic neuropathy was among the neurological disorders that Lal
listed for treatment. (Id. at col. 20, l. 61.)
11. According to Lal:
a) “HUTRAN-1 activity may be demonstrated by the ability to
convert L-phenylalanine and α-keto-γ-methiolbutyrate to
phenylpyruvate and L-methionine” (id. at col. 38, ll. 55-57);
b) “HUTRAN-2 activity may be demonstrated by the ability to
convert L-glutamate and α-ketoadipate to α-aminoadipate and α-
ketoglutarate” (id. at col. 39, ll. 2-4); and
c) “HUTRAN-3 activity may be demonstrated by the ability to m
ethylate hnRNP A1 protein in vitro” (id. at col. 39, ll. 25-26).
Appeal 2010-000898
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Principles of Law
“Rejections 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.” In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006), cited with
approval in KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 417-18 (2007).
When identifying a reason for modifying a prior art compound, “‘it is
sufficient to show that the claimed and prior art compounds possess a
‘sufficiently close relationship . . . to create an expectation,’ in light of the
totality of the prior art, that the new compound will have ‘similar properties’
to the old.’” Eisai Co. Ltd. v. Dr. Reddy’s Labs., Ltd., 533 F.3d 1353, 1357
(Fed. Cir. 2008) (quoting Aventis Pharma Deutschland GmbH v. Lupin, Ltd.,
499 F.3d 1293, 1301 (Fed. Cir. 2007) (quoting In re Dillon, 919 F.2d 688,
692 (Fed. Cir. 1990)).
An obviousness rejection based on similarity in chemical
structure and function entails the motivation of one skilled in
the art to make a claimed compound, in the expectation that
compounds similar in structure will have similar properties. . . .
When prior art compounds essentially “bracketing” the claimed
compounds in structural similarity are all known as pesticides,
one of ordinary skill in the art would clearly be motivated to
make those claimed compounds in searching for new pesticides.

In re Payne, 606 F.2d 303, 313-14 (CCPA 1979) (internal citations omitted).

Analysis
The Examiner found the selection of Appellants’ elected compound to
have been simply a matter of picking and choosing from Pharmacia’s
“various substituents with the expectation the resulting compounds will have
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Application 10/497,491

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the desired effect in varying degrees.” (Ans. 5.) Because Pharmacia taught
that all the compounds included in its genus would be kynurenine-3-
hydroxylase inhibitors (FF 1), we agree. As the Examiner noted, this is not a
case where evidence of unexpected results has been offered to show that a
particular selection from Pharmacia’s genus would have been nonobvious.
In this circumstance, Pharmacia’s explicit disclosure was sufficient evidence
to create an expectation that the compounds in its genus, including
Appellants’ choice, would have the expected properties. See Eisai, 533F.3d
at 1357. Put another way, Pharmacia’s disclosure also bracketed the species
Appellants chose with structurally similar compounds that all had the same
function. See Payne, 606 F.2d at 313-14. We are not persuaded of error on
that ground.
The rejection on appeal is also based on a finding that Lal taught
administering a compound that could stop the conversion of kynurenine to
kynurenic acid to treat diabetic neuropathy. (FF 6.) We do not see that idea
explicitly stated in Lal, and the Examiner has not explained how Lal can be
read as implicitly disclosing it. We agree with the Examiner that Lal’s
“Background of the Invention” discusses some enzymes that act in
kynurenine metabolism (FF 7 and 8), but we see no teaching to administer
them. Instead, Lal taught administering HUTRAN-1, -2, or -3, which are
said to be transferase enzymes. (FF 9.) The Examiner has not provided
evidence or explained that a person of ordinary skill would have understood
Lal to disclose that any of the HUTRANs could stop the kynurenine
reaction. On this record, we conclude that the rejection is insufficient to
support a conclusion of obviousness.

Appeal 2010-000898
Application 10/497,491

9
CONCLUSIONS
A person of ordinary skill in the art would have selected any
compound from Pharmacia’s genus with the expectation that it would
function as Pharmacia taught.
The Examiner has not established that the content of Lal’s disclosure
supports the finding that Lal taught administering a compound that stops the
conversion of kynurenine to kynurenic acid as a treatment for diabetic
neuropathy.

SUMMARY
We reverse the rejection of claims 2, 3, 10, 11, 13, 15, 17-19, 22 and
23 under 35 U.S.C. § 103(a) as unpatentable over Pharmacia & Upjohn
S.O.A. (WO 97/17317) and Lai.

REVERSED

lp

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