Ex Parte Schwarcz et al

Patent Trial and Appeal Board

Sep 20, 2016

12742171 (P.T.A.B. Sep. 20, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
121742,171 05/10/2010
24239 7590 09/22/2016
MOORE & VAN ALLEN PLLC
P.O. BOX 13706
3015 Carrington Mill Boulevard, Suite 400
Research Triangle Park, NC 27709
FIRST NAMED INVENTOR
Robert Schwarcz
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
035413.319 2935
EXAMINER
BERNHARDT, EMILY A
ART UNIT PAPER NUMBER
1624
NOTIFICATION DATE DELIVERY MODE
09/22/2016 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):
iplaw@mvalaw.com
usptomail@mvalaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ROBERT SCHWARCZ, Y ASUSHI KAJII,
and SHIN-ICHIRO ON0 1
Appeal2015-001426
Application 12/742,171
Technology Center 1600
Before JEFFREY N. FREDMAN, JOHN G. NEW, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
NEW, Administrative Patent Judge.
DECISION ON APPEAL
1Appellants state the real party-in-interest is the University of Maryland,
Baltimore. App. Br. 3.
Appeal2015-001426
Application 12/742,171
SUMMARY
Appellants file this appeal under 35 U.S.C. § 134(a) from the
Examiner's Final Rejection of claims 23 2 as unpatentable under 35 U.S.C.
§ 103 (a) as being obvious over the combination of Schriewer et al. (US
5,237,060, August 17, 1993) ("Schriewer"), Desideri et al. (US 4,758,567,
July 19, 1988) ("Desideri"), and Ueda et al. (US 5,591,744, January 7, 1997)
("Ueda").
We have jurisdiction under 35 U.S.C. § 6(b)
We AFFIRM.
NATURE OF THE CLAIMED INVENTION
Appellants' invention is directed to compounds of formula (I),
prodrug derivatives and/or pharmaceutically acceptable salt thereof, which
selectively inhibit the enzyme kynurenine aminotransferase, thereby
reducing the synthesis of kynurenic acid. The compounds are used for the
treatment of psychiatric and neurological diseases which benefit from an
increase in glutamatergic and/or cholinergic neurotransmission, such as
schizophrenia, depression, bipolar illness, anxiety and Alzheimer's disease.
Furthermore, the compounds of the invention are useful for stimulating
attention, memory and other cognitive processes in normal individuals of
any age, including children, adolescents and the elderly. Additionally, the
compounds of the invention are also useful for treatment of patients
suffering from malaria by preventing parasite gametogenesis and fertility
2 Claims 1-22 and 24 are canceled. App. Br. 22.
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Application 12/742,171
based on reduction of xanthurenic acid formation from its bioprecursor 3-
hydroxy kynurenine. Abstract.
REPRESENTATIVE CLAIM
Claim 23 is the sole claim on appeal, and recites:
23. A compound having the following structure:
("~
:-:;_·
r ···y,,.,··\:c:t·)\~./ <::<\+:::
:~·······'',N.)t,{,,,~J' 4 _})
·:: :· ~ ~
*'~'JN·'· N ... ,, ...• ) 0 ·,,'", .... ,
and is (S)-(-)-9-( 4-Aminopiperazin-l-yl)-8-fluoro-3-methyl-6-oxo-2,3-
dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid, (S)-(-)-9-( 4-
Aminopiperazin-1-y 1 )-8-fluoro-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa
-3a-aza-phenalene-5-carboxylic acid ethyl ester or a pharmaceutically
acceptable salt thereof in an effective amount to inhibit the synthesis of
kynurenic acid.
App. Br. 22.
ISSUES AND ANALYSIS
We agree with, and adopt, the Examiner's findings and conclusion
that the appealed claim is prim a facie obvious over the cited prior art
references. We address the arguments raised by Appellants below.
Issue 1
Appellants argue the Examiner erred in finding the combined cited
prior art teaches or suggests all of the limitations of claim 23. App. Br. 7.
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Application 12/742,171
Analysis
Appellants point to each of the references in tum, arguing that none of
them, singly or in combination with the others, teaches or suggests all of the
limitations of claim 23. App. Br. 7.
With respect to Desideri, Appellants argue that the basic structure
taught by Desideri is as follows:
~~~~=-
.& ~ :N ~~r .~ .. :c: ....... f-;;
Y i:i K > K>--:f ~i~ :>('::fl;
.~ i:; .:$. (\ .. ·{~ .. ~~~}~ ::~' t~:~---t~~ '-'=)·~:~~~):} ~~x~~;
ll.~ ~ m~':I:;~~ (~;~ ·~~~ §~'7~:'$~} ..:.:X':>.~~t~§ ~rf-:-l {~~~7:'th~
~®I.., ® -:mtioo gt¢%' -ru:· s y,.-m~ -of fo1:~m.~l~~
~}",(~~!«'~"'
w~~··~k~ -~~. ~s ~ (\ ..... t>~:- ~~~~\~~i. <~t ~~~~~~zj ~*''
~~:$ ~~~® ,~f ~~l '~~)..~~~~ .. *~~~~~~'°· &~~~~w
,":-l. ~~~~~~>*~X~~~~~~~~ ~:t,:~~~ ....
The basic structure claimed by Desideri as recited in column 1, lines 13-33
Additionally, Appellants point to Example 5 of Desideri, which, when
read in light of Example 3 and upon which the Examiner relies, teaches the
following structure:
,,
. :>:·:·
... n ...
The structure of Examples 3 and 5 of Desideri (N-amino--norfloxacine)
as depicted in Examiner's Answer at 3.
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Application 12/742,171
App. Br. 8. Appellants point out that although this structure possesses an
amino group on the piperazine ring, this and all of the embodiments claimed
by Desideri lack the requisite morpholine ring as shown in claim 1.
Appellants point next to Schriewer, which teaches, inter alia, the
following structure:
\. l\
\..,,,,,,,,,~
The structure taught by Schriewer at column 20, lines 2-11
App. Br. 9 (citing Schriewer Exs. 4, 16). Appellants contend Schriewer is
directed to methods of synthesizing the antibiotic ofloxacin, which
necessarily requires that a methyl group be attached to the piperazine ring,
rather than an amino group, as required by claim 23. Id. Consequently,
argue Appellants, there is no teaching or suggestion in Schriewer that would
direct a person of ordinary skill to replace the "important" methyl (i.e.,
"alkyl") group on the piperazine ring. Id. Appellants also contend there is
no direction in either Desideri or Schriewer that would inform a person of
ordinary skill which elements of each reference to combine and which to
delete. Id. at 10.
Appellants next point to the Examiner's citation to Ueda, which
Appellants argue adds nothing relevant to the teachings of Desideri and
Schriewer. App. Br. 11. Ueda teaches the following basic structure:
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Appeal2015-001426
Application 12/742,171
Novel antimicrobial benzoheterocyclic compound taught by Ueda
at column 1, lines 7-13.
Appellants admit that Ueda teaches substitution at the R2 position is
defined as a 5 to 9-membered saturated or unsaturated heterocyclic ring
which may be substituted by, inter alia, an amino-substituted piperazine
ring, as recited in claim 1. App. Br. 14. However, Appellants argue, that
substitution is contained in six columns of possible substitutions. App. Br.
11-13 (quoting Ueda cols. 3-9, 11. 18-21 ). Appellants argue that a person of
ordinary skill would not have motivation to extract this embodiment from
the list without using Appellants' Specification as a map to arrive at the
claimed composition.
Appellants argue that, to successfully demonstrate that a new
compound is obvious, the Examiner must show "that the prior art would
have suggested making the specific molecular modifications necessary to
achieve the claimed invention." App. Br. 15 (quoting Takeda Chemical
Industries Ltd. v. Alphapharm Pty. Ltd., 492 F.3d 1350, 1356 (Fed. Cir.
2007)). Therefore, Appellants argue, in addition to structural similarity
between the compounds, a prim a facie case of obviousness may be shown
by "adequate support in the prior art" for the change in structure. Id.
(quoting In re Grabiak, 769 F.2d 729, 732 (Fed. Cir. 1985)). As such,
Appellants assert, the Examiner must identify some reason that would have
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Application 12/742,171
led a chemist to modify a known compound, to establish a prima facie case
of obviousness for a new claimed compound. Id.
The Examiner responds that, given that both the 4-amino group on the
piperazine ring and tricyclic core features of Appellants' invention are
explicitly taught in the references, one skilled in the art would have been
motivated to replace the 4-methyl of Schriewer' s compounds with a 4-amino
or, alternatively, replace the quinoline core of Desideri with the instant core
in view of the combined teachings outlined above.
We are not persuaded by Appellants' arguments. Schriewer teaches a
composition that is essentially identical to Appellants' claimed composition
with the single exception that the 4-substituted methyl group on the
piperazine ring of Schriewer has been substituted with an amino group in the
composition of claim 23. We agree with the Examiner that such a simple
substitution would have been obvious to a person of ordinary skill in the art
and that the compound of Schriewer would have reasonably been selected as
a lead compound. The case law of our reviewing court has consistently held
that a simple substitution in an otherwise obvious prior art molecule is
insufficient to render the molecule nonobvious. See, e.g., In re Dillon, 919
F.2d 688, 696 (Fed. Cir. 1990) ("[I]f 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 ... a
primafacie case of obviousness." (citing In re Henze, 181 F.2d 196
(C.C.P.A. 1950); In re Hass, 141 F.2d 122, 127, 130 (C.C.P.A. 1944))); see
also In re Shetty, 566 F.2d 81, 85-86 (C.C.P.A. 1977) (concluding that "the
difference of a mere methylene group between the compound of the claim
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Appeal2015-001426
Application 12/742,171
and the prior art compounds" is obvious); Jn re Bowers, 359 F.2d 886, 887
(C.C.P.A. 1966).
We note that this case also differs from Takeda because in Takeda
there was substantial evidence presented that the claimed compound
"pioglitazone exhibited unexpectedly superior properties over the prior art
compound b." Takeda, 492 F.3d at 1361. There is no such evidence of
unexpected results, or indeed of any results, present in the instant application
comparing the claimed composition with Schriewer' s disclosed compound.
This analysis is consistent with Wilder, where the court found that "one who
claims a compound, per se, which is structurally similar to a prior art
compound must rebut the presumed expectation that the structurally similar
compounds have similar properties." In re Wilder, 563 F.2d 457, 460
(CCP A 1977).
Furthermore, we are not persuaded by Appellants' argument that: "the
compound of Schriewer MUST include an alkyl substituted piperazine ring
to have the activity of the copied Ofloxacin." App. Br. 9-10, 15. We agree
with Appellants that the 4-methyl-substituted piperazine compound
described in Schriewer, and depicted supra, corresponds to ofloxacin, which
is further described as having antibiotic properties in Examples 4 and 16.
However, we decline to read the teachings of Schriewer so narrowly. Rather
than being limited to teaching solely a method for the synthesis of ofloxacin,
Schriewer is directed to: "a process for the preparation of highly
antibacterially-active enantiomerically-pure 1,8-bridged 4-quinolone-3-
carboxylic acids and derivatives." Schriewer Abstr. Schriewer is directed to
the synthesis of a large genus of compounds, some of which have
antibacterial activity. However, Appellants adduce no evidence teaching or
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Appeal2015-001426
Application 12/742,171
suggesting that a 4-methyl-substituted piperazine ring is an absolute or
unalterable requirement of the compounds taught by Schriewer, as
Appellants argue. In fact, claim 2 of Schriewer recites, in relevant part:
2. A process for the preparation· of an enantiomerically pure
1,8-bridged 4-quinoione-3-carboxyiic acid and derivatives
thereof according to claim 1, wherein a 10-( 1-piperazinyl)
compound (with n=[O]) or 11-(1-piperazinyl) compound (with
n=l) of the formula
in which the piperazinyl radical can be mono-, di- or tri-
substituted on the carbon atoms by C1-C4-alkyl, 2-thienyl or
optionally substituted cyclohexyl or phenyl ....
(emphasis added). Although not explicitly teaching an amino substitution at
the C4 location on the piperazine ring, Schriewer does not require a methyl
group at that location, contrary to Appellant's assertion. Indeed, the
compound depicted in claim 2 has a hydrogen ion at that locus. We
consequently agree with the Examiner's conclusion that substitution of an
amino group for a methyl group at that location would have been obvious to
a person of ordinary skill in the art.
Issue 2
Appellants next argue that their claimed compound is not obvious
because it unexpectedly inhibits kynurenine-aminotransferase II (KAT II)
activity, and thus, inhibits the synthesis ofkynurenic acid. App. Br. 18.
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Analysis
Appellants assert there is nothing in the prior art that teaches the
inhibitory activity of the compound of claim 23, and the Examiner cannot
arrive at this finding by relying upon something that is not disclosed. App.
Br. 18-19. According to Appellants, obviousness cannot be predicated on
what is not known at the time an invention is made, even if the inherency of
a certain feature is later established. Id. at 19 (citing In re Rijckaert, 9 F.3d
1531, 1534 (Fed. Cir. 1993)). Here, Appellants argue, the ability to inhibit
kynurenine-aminotransferase II (KAT II) activity which inhibits the
synthesis of kynurenic acid was heretofore unknown. Id. Therefore,
Appellants assert, a skilled artisan could not make any modification to arrive
at an invention that possesses previously unknown characteristics. Id.
Appellants point to their Specification, which discloses an in vivo
example showing the effectiveness of the claimed compound. App. Br. 19.
Appellants point to Figure 2 of the Specification, which they argue
demonstrates that administration of their claimed compound reversibly
reduces extracellular kynurenic acid (KYNA) levels by about 40% and
simultaneously increased extracellular dopamine (DA) levels >2.5-fold. Id.
at 20. Therefore, Appellants argue, the presently claimed compound
possesses unexpected properties that were unknown in the prior art. Id.
The Examiner responds that Appellants' discovery of an additional
property does not make otherwise obvious compounds nonobvious. Ans. 5.
Rather, the Examiner states, Appellants must prove that their composition
possess a property that the prior art compound(s) do not possess, and not one
that they are not disclosed to possess. Id.
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The Examiner further finds it is Appellants' burden to show that their
claimed compounds possess an unexpected property or improvement that is
not shared by the prior art compounds. Ans. 13. The Examiner finds the
data presented in Appellants' Specification is not a comparative showing
with the closest species in the prior art; therefore it does not address the
rejection, much less overcome it. Id. at 14.
We agree with the Examiner. As an initial matter, claim 23 is directed
to: "A compound having the following structure .... " As such, the plain
language of the claim demonstrates that the claim is directed to a
"composition of matter" (emphasis added) and not to a method or process.
Consequently, the language recited in the concluding limitation of the claim
"in an effective amount to inhibit the synthesis of kynurenic acid" does not
directly or indirectly describe a structural feature of the claimed
composition, but rather describes an intended use of the compound, i.e., to
inhibit the synthesis of kynurenic acid. Such claim language sets forth the
intended use for, or a property inherent in, an otherwise obvious
composition, but does not differentiate the claimed composition from those
known to the prior art. See In re Pearson, 494 F.2d 1399, 1403 (C.C.P.A.
1974) (citing Kropa v. Robie, 187 F.2d 150 (1951); In re Lemin, 326 F.2d
437 (1964); and In re Zierden, 411F.2d1325 (C.C.P.A. 1969)).
Furthermore, we have explained supra our reasons for concluding that
the compound recited in claim 23 is obvious over the teachings of the cited
prior art. In cases in which "the claimed and prior art products are identical
or substantially identical in structure or composition, or are produced by
identical or substantially identical processes, a prima facie case of either
anticipation or obviousness has been established." MPEP § 2112.0l(I)
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(citing Jn re Best, 562 F.2d 1252, 1255 (C.C.P.A. 1977)). "Where, as here,
the claimed and prior art products are identical or substantially identical, or
are produced by identical or substantially identical processes, the PTO can
require an applicant to prove that the prior art products do not necessarily or
inherently possess the characteristics of his claimed product." Best, 562
F.2d at 1255. Therefore, the Examiner's primafacie case of obviousness
can be rebutted by evidence showing that the prior art products do not
necessarily possess the characteristics of the claimed product. Id. (citing In
re Best, 562 F.2d at 1255); see also Titanium Metals Corp. v. Banner, 778
F.2d 775 (Fed. Cir. 1985) (holding that if a composition is the same as the
prior art, it is immaterial what properties they have or who discovered the
properties because the composition must necessarily exhibit the properties).
Appellants have demonstrated that their claimed compound can
inhibit the synthesis of kynurenic acid. See Spec. Ex. 11; Fig. 2. However,
Appellants have not met their burden of showing that this property of the
claimed compound is unexpected over the prior art, e.g., the compounds
disclosed and rendered obvious by the combined cited prior art. Appellants
argue that the compounds cited in the prior art, and especially Schriewer
possess antibiotic properties, but have not been shown to inhibit synthesis of
kynurenic acid. App. Br. 9. Appellants provide no evidence that
Schriewer's compound does not inhibit kynurenic acid synthesis, only that
the compound was not tested. But Appellants have not claimed a method of
inhibiting kynurenic compound, rather, Appellants have claimed a
compound that has the intended purpose of inhibiting kynurenic acid. And,
as we have explained, such an intended purpose is not limiting on the claims
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Finally, the limitation reciting "in an effective amount to inhibit the
synthesis of kynurenic acid" recites no amount or concentration of the
claimed compound which would be sufficient to inhibit the synthesis of
kynurenic acid, or under what circumstances. As such, the limitation cannot
be said to be limiting upon the scope of the claim.
Consequently, we agree with the Examiner's conclusion that claim 23
is obvious over the combined cited prior art and we therefore affirm the
Examiner's rejection of the claim.
DECISION
The Examiner's rejection of claim 23 as unpatentable under 35 U.S.C.
§ 103(a) is affirmed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l). See 37 C.F.R.
§ 1.136(a)(l )(iv).
AFFIRMED
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