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`IN THE UNITED STATES EATEET AND TRADEMARK OFFICE
`BEFORE THE BOARD or PATENT AEPEALS AND INTERFERENCES
`
`25W’
`
`WATTANASIN,
`
`v.
`
`PICARD et al-
`
`v.
`
`FUJIKAWA et al
`
`INTERFERENCE N0. :
`
`102,648
`
`EXAHINER¥IN-CHIEF:
`
`MICHAEL SOFOCLEOUS
`
`FUJIKAWA ET AL REPLY TO THE OPPOSITION
`A TO FUJIKAWA ET AL'S MOTION TO ADD COUNTS 3 AND 4
`
`HONORABLE COMISSIONER OF PATENTS AND TRADEMARKS“
`WASHINGTON, D.C.
`20231
`
`BOX INTERFERENCE '
`
`~SIR:
`
`In opposition to Fujikawa’s Motion to Add Counts 3 and 4, and
`add claims to the Wattanasin appiication, Wattanasin essentially
`
`urges three different grounds of opposition. First, Wattanasin
`
`insists that the claims proposed by Fujikawa for the Wattanasin
`
`application, that correspond to Counts 3 and 4, are not patentable
`to Wattanasin, Wattanasin lacking a written description the same,
`
`35 U.S.C. 112, first paragraph. Second, Wattanasin urges that the
`
`Mylan Exhibit 1031, Page 1
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`Mylan Exhibit 1031, Page 1
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`
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`
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`evidence submitted. with the Fujikawa. Motion is inadequate to
`
`demonstrate that the subject matter of Counts 3 and 4 is directed
`
`to subject matter patentably distinct from Counts 1 and 2 in the
`interference.
`Third, Wattanasin objects to the Motion on the
`
`grounds that Fujikawa's Clahm 18 is directed to subject matter
`closely related to the subject matter of Counts 3 and 4, and not
`
`shown to be patentably distinct therefrom.
`
`Each of the arguments
`
`is replied to, below.
`
`I. Written Description in Wattanasin's Application
`
`Wattanasin urges that Fujikawa's proposed Claims 11 and 12 for
`
`the Wattanasin application are unsupported by"
`
`the Wattanasin
`
`disclosure,
`
`in that they lack a written description.
`
`It is to be
`
`particularly noted that the contentions of Wattanasin are unsup-
`
`ported by proof of any kind, and that
`
`in fact the evidence of
`
`record,
`
`including admissions by Wattanasin, supports the opposite
`
`conclusion.
`
`In exploring any question of written description, attention is
`
`focused on whether or not the specification, as originally filed,
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`Mylan Exhibit 1031, Page 2
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`
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`Mylan Exhibit 1031, Page 2
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`
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`conveys
`
`to those of skill
`
`in ‘the art
`
`that
`
`the inventors had
`
`possession of the invention at the time the application was filed.
`
`Quite conspicuously, any testimony from the inventors,
`
`regarding
`
`their possession of this invention, is absent from the Wattanasin
`
`opposition. Note that the standard for determining compliance with
`
`written description, whether or not those of skill in the art would
`
`conclude that applicants had possession of the invention at the
`
`time of filing, has been long established.
`
`In re Smith,
`
`178
`
`U.S.P.Q. 620 (C.C.P.A. 1973). Thus, the sole inquiry presented to
`
`the Board on this issue is whether or not one of ordinary skill in
`
`tthe art,
`
`reading the Wattanasin disclosure, would conclude that
`
`Wattanasin had possession of the invention addressed in Claims 11
`and 12 at the time the Wattanasin application was filed.
`
`The sole limitation of proposed Claims 11 and 12 Wattanasin
`
`urges
`is pg; described in the Wattanasin application is the
`identity of substituent R as cyclopropyl. Wattanasin urges that
`
`’there is no specific recitation or exemplification of this species.
`
`Fujikawa agrees, but notes that
`the same is not required for
`written description.
`In re Kaslow, 217 U.S.P.Q. 1089, 1996 (Fed.
`
`Cir.
`
`1983)
`
`and cases cited therein.
`
`Specifically, Wattanasin
`
`discloses that the substituent at the 2—position may be cycloalkyl
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`Mylan Exhibit 1031, Page 3
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`Mylan Exhibit 1031, Page 3
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`
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`
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`
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`of 3-7 carbon atoms.
`
`This identifies a class of five possible
`
`substituents.
`
`The class is not all
`
`that
`
`large,
`
`and Fujikawa
`
`submits that, without more, one of ordinary skill in the art would
`
`clearly conclude that the compound of Claim 11, and process of
`
`Claim 12, was clearly within the scope of the invention discovered
`
`by Wattanasin at the time of filing.
`
`Indeed, Wattanasin urges the
`
`same. See page 6 of the Opposition. Under similar circumstances,
`
`courts of competent jurisdiction have repeatedly held that selec-
`
`tion of one among five is clearly supported, for the purposes of
`
`written description.
`
`In re Driscoll, 195 U.S.P.Q. 434 (C.C.P.A.
`
`1978)
`
`(one of 14); and In re Johnson, 194 U.S.P.Q. 187, 195-96
`
`(C.C.P.A. 1977)
`
`(a reduction of
`
`from 12 to 10 members clearly
`
`‘supported).
`
`While prior.cases may be of
`
`limited value in determining
`
`compliance with the written description provision.of 35 U.S.C. 112,
`
`first paragraph, it is respectfully submitted that, without more,
`
`prior cases have held that the selection of one member of a class
`
`of five, when that member is encompassed by the generic disclosure,
`
`is supported by that generic disclosure, in the absence of counter-
`
`vailing evidence. Clearly, one of ordinary skill in the art taught
`
`that the substituent at the 2-position may be any one of cyclo-
`
`Mylan Exhibit 1031, Page 4
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`
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`Mylan Exhibit 1031, Page 4
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`
`
`
`
`
`
`propyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl would
`
`clearly conclude that cyclopropyl is within the province of the
`
`invention of Wattanasin.
`
`Indeed, it is the likely starting point,
`
`having the lowest molecular weight. More is not required.
`
`Beyond
`
`that,
`
`however, Wattanasin acknowledges
`
`that
`
`the
`
`Wattanasin application repeatedly exemplifies isopropyl.
`
`Indeed,
`
`isopropyl is mentioned by name as an alternate substituent at the
`
`2-position. Having been taught that isopropyl is an acceptable
`substituent and within the scope of Wattanasin’s invention,
`those
`
`of skill
`
`in the art would readily arrive at
`
`the selection of
`
`cyclopropyl, out of the disclosure of cycloalkyl of 3-7 carbon
`
`atoms, as the next logical, and analogous compound,
`
`isomerically
`
`related to exemplified species. Clearly,
`
`in the given case, there
`
`is more than simple narrowing of the Wattanasin claims from a genus
`
`of five to a sub-genus of one. Here there is additional supportive
`
`teaching that the isomer of that sub-genus is also suitable.
`
`It is
`
`well established that isomeric species are expected to behave in
`
`similar fashion, in the absence of evidence to the contrary. Those
`
`of skill
`
`in the art would certainly consider cyclopropyl
`
`to be
`
`within the scope of the compound and processes taught and claimed
`
`by Wattanasin.
`
`Mylan Exhibit 1031, Page 5
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`
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`Mylan Exhibit 1031, Page 5
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`
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`
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`
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`The Wattanasin argument that there is no written description
`lof the claims in question, Claims 11 and 12, must be rejected. The
`
`"selection", urged by Wattanasin to be totally beyond those of
`
`ordinary skill in the art,
`
`is simple, straightforward, and addi-
`
`tionally supported by the selection of isopropyl as an alternate
`
`substituent in the disclosure of Wattanasin.
`
`If
`
`further
`
`evidence were
`
`required,
`
`it
`
`is provided by
`
`Wattanasin. Wattanasin urges, pages 8-9 of its Opposition,
`
`that
`
`those of skill in the art were well aware that both isopropyl and
`
`cyclopropyl substituents could be employed in a similar position on
`
`related compounds.
`
`Specifically, Wattanasin relies on European
`
`Patent Publication 179,559. Regardless of what that publication
`actually teaches,
`there is a clear admission, on the part of
`
`Wattanasin, pages 8-9, that those of skill in the art, reading the
`
`Wattanasin application, would be aware that wherever isopropyl is
`
`taught for substitution next
`to the nitrogen atom on the ring,
`cyclopropyl may be similarly employed (note, as discussed below,
`
`Fujikawa does not agree that the art teaches that one would expect
`
`particular improvements in going from isopropyl to cyclopropyl in
`
`the subject matter of the claims of Wattanasin and Fujikawa).
`
`It
`
`is sufficient, for the issue of written description, to note that
`
`Mylan Exhibit 1031, Page 6
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`
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`Mylan Exhibit 1031, Page 6
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`
`
`
`
`
`
`those of ordinary skill in the art would be aware that given a
`
`A teaching of
`
`isopropyl
`
`as
`
`an appropriate substituent
`
`for
`
`the
`
`position in question, one of skill in the art, taught that cyclo-
`
`alkyl of 3 carbon atoms was acceptable, would move to cyclopropyl.
`
`Again, Wattanasin’s argument undercuts its position, and grant of
`
`the Fujikawa Motion is respectfully solicited.
`
`II.
`
`The Evidence Offered in Support is Inadequate to.Make Out
`Patentable Distinction
`
`Fujikawa agrees with ‘Wattanasin that it is incumbent on
`
`Fujikawa to demonstrate that the subject matter of Counts 3 and 4
`
`is patentably distinct from the subject matter of Counts 1 and 2.
`
`Evidence of that patentable distinction is made out in the Declara-
`
`tion of Kitahara submitted with the Fujikawa Motion.
`
`Fujikawa
`
`submits herewith the Supplemental Declaration of Kitahara, provid-
`
`ing similar evidence for the lactone species, Test B. As made out
`
`in paragraph.
`
`2 of
`
`the Declaration,
`
`this data simply' was not
`
`available at the time of filing of the Fujikawa Motion.
`It is
`submitted herewith,
`in completion of the evidential burden placed
`
`on Fujikawa to demonstrate patentable distinction.
`
`Mylan Exhibit 1031, Page 7
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`
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`Mylan Exhibit 1031, Page 7
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`
`
`
`
`Wattanasin urges that the type of evidence presented does not
`
`make out
`
`an unexpected difference between the isopropyls and
`
`cyclopropyl classes (in the language adopted in the Wattanasin
`
`Opposition, the cyclopropyl class is the class of proposed Counts 3
`
`and 4, while the isopropyl class is the class of current Counts 1
`
`and 2).
`
`The Wattanasin position, unsupported by any evidence of
`
`record,
`
`is that
`
`the type of differences
`
`set
`
`forth, uniform
`
`_ superiority for the cyclopropyl class independent of substituent Z
`
`identity and test type, would be expected by those of ordinary
`skill in the art. Quite simply, the position adopted.by Wattanasin
`
`is contrary to the expectations of those of ordinary skill in the
`
`art.
`
`As made out
`
`in the Kitahara Declaration and Supplemental
`
`Declaration, regardless of the identity of moiety Z,
`
`the cyclo-
`
`propyl class is always more than twice as active as the closely
`
`related isomeric species isopropyl and n—propyl.
`
`Indeed, for the
`
`sodium salt, the Icw value for isopropyl is about 2.5 times greater
`
`than that for cyclopropyl, and the ICW value for n-propyl is 22
`
`times greater than that of cyclopropyl. Where other values for Z
`
`are considered,
`
`the comparison is even more‘drastic,
`
`the calcium
`
`salt cyclopropyl species having a five—fold greater activity,
`
`the
`
`Mylan Exhibit 1031, Page 8
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`
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`Mylan Exhibit 1031, Page 8
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`
`
`
`
`
`
`ethyl ester species having a fourteen-fold greater activity, and
`
`the lactone activity, again as measured by Test A, being nearly
`
`four times higher.
`
`When the alternative test, Test B,
`
`is given,
`
`the relative
`
`values are similar. Further, Kitahara, one of particular skill in
`
`this art,
`
`concludes
`
`in both the Supplemental Declaration and
`
`original Declaration that such increased activity could not have
`
`been predicted on the basis of structure alone. While Wattanasin
`
`urges to the contrary,
`
`the Wattanasin position is unsupported by
`
`any evidence of any type. Attorney argument, alone,
`
`is not an
`
`adequate substitute for proof.
`
`The Wattanasin position must be
`
`rejected.
`
`Wattanasin also urges that the level of skill in the art, as
`
`V reflected by European Patent Publication 179,559 and U.S. Patent
`
`4,925,852, would have predicted the differences obtained and
`
`reported in the Kitahara Declarations.
`
`Initially, it must be noted
`
`that U.S. Patent 4,925,852 is not part of the prior art, and not
`
`appropriate for consideration as to the level of skill brought to
`
`the question by artisans prior
`
`to the Fujikawa filing date.
`
`Specifically,rWattanasin urges that
`
`this patent was
`
`in the art
`
`prior to Fujikawa’s assertion herein of patentable distinction and,
`
`Mylan Exhibit 1031, Page 9
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`
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`Mylan Exhibit 1031, Page 9
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`
`
`
`
`
`
`-10..
`
`~ accordingly, must be considered. No legal support is provided, and
`
`Wattanasin’s position is contrary to specific holdings on this
`
`issue.
`
`It is well established that facts, determined at a date
`
`after
`
`filing,V are permissible to support
`
`a
`
`finding of non-
`
`obviousness as to compounds and processes, at the time of filing.
`
`Kansas Jack,
`
`Inc. v. Kuhn, 219 U.S.P.Q.
`
`857
`
`(Fed. Cir. 1983).
`
`Thus, the U;S. patent relied on by Wattanasin must be ignored, and
`
`attention focused only on the European patent publication.
`
`European Patent Publication 179,559 is confined to compounds
`
`and processes patentably distinct
`
`from the compounds claimed
`
`herein.
`
`The formulas are substantially unrelated. Note that the
`
`European patent publication is confined to trans-6-[2-substituted-
`
`pyrrol-1—yl)alkyl]-pyran-2-ones, thus, compounds quitevunrelated to
`the phenyl—substituted,
`lactone—substituted quinolines of
`the
`
`claimed invention.
`
`It is respectfully submitted that Wattanasin
`
`Mylan Exhibit 1031, Page 10
`
`
`
`Mylan Exhibit 1031, Page 10
`
`
`
`
`
`
`
`-11-
`
`has
`
`failed to :make out any art-recognized. equivalency’ between
`
`phenyl-substituted quinolines and the pyrroles of the reference.
`Indeed,
`review" of
`the file history" of U.S. Patent 5,011,930
`
`reflects the conclusion of Fujikawa and the Patent Office that,
`
`without evidence of any type,
`
`the subject matter of Counts 3 and 4
`
`and
`the disclosure of
`the European patent publication are
`patentably distinct, one from the other.
`In the absence of such an
`
`art-recognized equivalence, Wattanasin’s
`defective.
`1
`
`argument
`
`is
`
`fatally
`
`Moreover,
`
`Fujikawa
`
`respectfully submits
`
`that Wattanasin
`
`deliberately, and without support, misrepresents the teaching of
`
`the European patent publication. Specifically, Wattanasin urges,
`in the last paragraph on page 9 and first paragraph of page 10 of
`
`its Opposition, that this European patent publication teaches that
`
`one of skill in the art would expect "particular improvements in
`
`activity relative to a genus of compounds with the same series."
`
`Further, Wattanasin urges that one of ordinary skill in the art
`
`would have expected the cyolopropyl species to be better than the
`
`isopropyl species. No such teaching appears in the European patent
`publication.
`» Indeed, at best,
`the European patent publication
`
`identifies isopropyl and cyclopropyl as equivalent.
`
`See, e.g.,
`
`Mylan Exhibit 1031, Page 11
`
`
`
`Mylan Exhibit 1031, Page 11
`
`
`
`
`
`
`
`_ 12 _
`
`page 8,
`
`lines 30-35, wherein these two species are identified as
`
`equivalent. Many other preferences in the European.patent publica-
`
`A tion identify isopropyl as preferred to the cyclic species.
`
`See
`
`the sixth preferred genus, page 9, line 31 — page 10, line 12; the
`
`fifth preferred genus, particularly, page 9,
`
`lines 28-30;
`
`the
`
`fourth, page 7, line 29; and the second, page 7, line 20.
`
`Indeed,
`
`only the
`
`first
`
`and
`
`third preferences
`
`equate
`
`isopropyl
`
`land
`
`«cyclopropyl. Accordingly, it is respectfully submitted that the
`
`only‘ reference ‘Wattanasin submits that. may’ be looked.
`
`to,
`
`the
`
`European patent publication, at best establishes isopropyl and
`cyclopropyl
`to be equivalent, and may indicate isopropyl
`to be
`
`superior.
`
`Further,
`
`it is respectfully’ submitted that
`
`in fact,
`
`the
`
`the European. Patent Publication relied upon by
`compounds of
`Wattanasin have a much higher activity when isopropyl, rather than
`
`cyclopropyl is used as a substituent at the identified position.
`
`Submitted herewith please find Roth et al, Journal of Medicinal
`Chemist
`, 1990, 33, pages 21-31, which, authored by the inventors
`
`identified in the European Patent Publication relied upon by
`Wattanasin in its Opposition, reflects the activities of certain of
`
`the compounds embraced by the European Patent Publication, EP 179-
`
`559.
`
`4
`
`Mylan Exhibit 1031, Page 12
`
`
`
`Mylan Exhibit 1031, Page 12
`
`
`
`
`
`
`
`- 13 _
`
`Particular attention is directed to page 25 of the reference,
`
`which shows, Table III, that the ICW value for compound 8x (trans-
`6- [ 2 [2— ( 4-flluoropphenyl )*-5- ( 1-methylethyl)41-H-pyrrol-1—yl]-ethyl]
`
`tetrahydro-4-hydroxy-2-H—pyran-2-one is 0.40, while the Icm value
`
`for the cyclopropyl
`
`isomeric counterpart
`
`(compound 8aa)
`
`is 2.2.
`
`Thus,
`
`the isopropyl species is 5.5 times more active, by Warner-
`
`Lambert’s
`
`own
`
`reckoning,
`
`than the corresponding cyclopropyl
`
`species.
`
`To the extent the Warner Lambert European Publication is
`
`relevant to the issue at all, it again suggests those of ordinary
`
`skill in the art would look to the isopropyl species to have higher
`
`activity than the cyclopropyl species. Rather than supporting the
`
`Wattanasin position, the Warner Lambert publication serves to only
`more clearly highlight
`the fact
`that
`the art would not expect
`higher activities in the cyclopropyl species designated for the
`
`Count of
`
`the Interference,
`
`clearly" drawing attention to the
`
`unexpected and unobvious nature of the proposed Counts 3 and 4.
`
`Certainly, at best, there is no teaching in the art anywhere
`
`that one of ordinary skill in the art would expect the cyclopropyl
`
`class to be superior, consistently so by better than a factor of
`
`two, regardless of the identity of the Z substituent.. This, it has
`
`been sworn to, could not have been predicted on the basis of
`
`Mylan Exhibit 1031, Page 13
`
`
`
`Mylan Exhibit 1031, Page 13
`
`
`
`
`
`
`
`; 14 _
`
`structure alone. Wattanasin offers no proof to the contrary, and,
`
`accordingly,
`
`the Wattanasin Opposition cannot succeed. Grant of
`
`the Motion is respectfully requested.
`
`III. Fujikawa's Claim 18
`
`On page 14 of the Opposition, in the final paragraph, prior to
`
`the Conclusion, Wattanasin makes reference to Fujikawa’s Claim 18,
`which is 21 4—chlorophenyl-substituted species.
`The Wattanasin
`
`reference to this claim is not clearly understood. Fujikawa has no
`
`data to indicate that the chlorine—substituted species is equiva-
`
`the record
`indeed,
`lent to the fluorine-substituted species, and,
`lacks disclosure of the same.
`‘The burden would be on Wattanasin to
`
`demonstrate to the contrary. Notwithstanding the above, should the
`
`Examiner find it appropriate, it would be acceptable to designate
`Claim 18 of the Fujikawa patent application as corresponding to
`
`Counts 3 and 4 of the interference.
`
`Mylan Exhibit 1031, Page 14
`
`
`
`Mylan Exhibit 1031, Page 14
`
`
`
`
`
`
`
`_ 15 _
`
`IV. Conclusion
`
`'The Wattanasin position is totally unsupported by evidence
`
`confirming
`
`the
`
`arguments
`
`offered by Wattanasin's
`
`counsel.
`
`Wattanasin, having urged that
`
`those of ordinary skill would
`
`recognize both isopropyl and cyclopropyl as suitable substituents
`
`at the 2-position in the compounds of the claimed invention, and
`
`having disclosed the suitability of both isopropyl and cycloalkyl
`of 3 carbon atoms as suitable substituents at that position, cannot
`
`successfully argue that Claims 11 and 12 proposed by Fujikawa are
`
`not supported by the written description of the Wattanasin appli-
`
`cation. Similarly, there is absolutely no evidence of record that
`suggests that the differences between the compounds of Counts 3
`
`and 4, proposed by Fujikawa, and Counts
`
`1 and 2,
`
`respectively,
`
`would be anywhere predicted by those of skill in the art.
`
`Indeed,
`
`the prediction would be quite to the contrary, that those of skill
`
`would expect similar performance, given the isomeric relationship
`
`of the compounds tested. Having successfully demonstrated patent-
`
`able distinction between Counts 3 and 4 and Counts 1 and 2, and
`
`having an appropriate claim for Wattanasin to contest priority with
`
`respect thereto, the Fujikawa Motion should be granted. Should the
`
`Mylan Exhibit 1031, Page 15
`
`
`
`Mylan Exhibit 1031, Page 15
`
`
`
`
`
`
`
`_ 15 -
`
`Examiner-in-Chief find it necessary, Claim 18 may be designated as
`
`corresponding to Counts 3 and 4, and benefit with respect thereto,
`
`on the grounds previously urged in Fujikawa's Motion for Benefit as
`
`to those counts, is respectfully requested.
`
`Respectfully submitted,
`
`OBLON, SPIVAK, MCCLELLAND,
`MAIER & NEUSTADT, P.C.
`
`even fig/helber
`
`30,073
`Registration No.:
`Attorney for Fujikawa et al
`
`Crystal Square Five
`Fourth Floor
`
`1755 Jefferson Davis Highway
`Arlington, Virginia 22202
`(703) 521-5940
`
`Mylan Exhibit 1031, Page 16
`
`
`
`Mylan Exhibit 1031, Page 16