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.
`
`F ING DATE
`
`FIRST NAMED INVENTOR
`
`ATTORNEY DOCKET NO.
`
`CONF {MATION NO.
`
`10/500,354
`
`06/30/2004
`
`Masayo Higashiyama
`
`2004_1016A
`
`2612
`
`513
`
`7590
`
`05/08/2009
`
`WENDEROTH, LIND & PONACK, L.L.P.
`1030 15th Street, N.W.,
`Suite 400 East
`
`Washington, DC 20005-1503
`
`EXAMINER
`
`RAE, CHARLESWORTH E
`
`ART UNIT
`
`1611
`
`MAIL DATE
`
`05/08/2009
`
`PAPER NUMBER
`
`DELIVERY MODE
`
`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)
`
`MYLAN EX. 1024, Page1
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`MYLAN Ex. 1024, Page1
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`

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`Office Action Summary
`
`Application No.
`
`App|icant(s)
`
`10/500,354
`
`HIGASHIYAMA, MASAYO
`
`Examine,
`
`CHARLESWORTH RAE
`
`A,, Unit
`
`1611 -
`
`-- The MAILING DA TE of this communication appears on the cover sheet with the correspondence address --
`Period for Reply
`
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE Q MONTH(S) OR THIRTY (30) DAYS,
`WHICHEVER IS LONGER, FROM THE MAILING DATE OF THIS COMMUNICATION.
`- Extensions of time may be available under the provisions of 37 CFR 1.136(a).
`In no event, however, may a reply be timely filed
`after SIX (6) MONTHS from the mailing date of this communication.
`If NO period for reply is specified above, the maximum statutory period will apply and will expire SIX (6) MONTHS from the mailing date of this communication.
`-
`- Failure to reply within the set or extended period for reply will, by statute, cause the application to become ABANDONED (35 U.S.C. § 133).
`Any reply received by the Office later than three months after the mailing date of this communication, even if timely filed, may reduce any
`earned patent term adjustment. See 37 CFR 1.704(b).
`
`Status
`
`1)IXI Responsive to communication(s) filed on 05 January 2009.
`
`2a)I:I This action is FINAL.
`
`2b)IXI This action is non-final.
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`3)I:I Since this application is in condition for allowance except for formal matters, prosecution as to the merits is
`
`closed in accordance with the practice under Ex parte Quayle, 1935 C.D. 11, 453 O.G. 213.
`
`Disposition of Claims
`
`4)IXI C|aim(s)i is/are pending in the application.
`
`4a) Of the above c|aim(s)
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`is/are withdrawn from consideration.
`
`5)I:I C|aim(s)
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`is/are allowed.
`
`6)IXI C|aim(s)i is/are rejected.
`
`7)I:I C|aim(s) j is/are objected to.
`
`8)I:I C|aim(s) j are subject to restriction and/or election requirement.
`
`Application Papers
`
`9)I:I The specification is objected to by the Examiner.
`
`10)I:I The drawing(s) filed on
`
`is/are: a)I:I accepted or b)I:I objected to by the Examiner.
`
`Applicant may not request that any objection to the drawing(s) be held in abeyance. See 37 CFR 1.85(a).
`
`Replacement drawing sheet(s) including the correction is required if the drawing(s) is objected to. See 37 CFR 1.121(d).
`
`11)I:I The oath or declaration is objected to by the Examiner. Note the attached Office Action or form PTO-152.
`
`Priority under 35 U.S.C. § 119
`
`12)I:I Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
`
`a)I:I All
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`b)I:I Some * c)I:I None of:
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`Certified copies of the priority documents have been received.
`
`Certified copies of the priority documents have been received in Application No.
`
`Copies of the certified copies of the priority documents have been received in this National Stage
`
`application from the International Bureau (PCT Rule 17.2(a)).
`
`* See the attached detailed Office action for a list of the certified copies not received.
`
`Attach ment(s)
`
`1) E Notice of References Cited (PTO-892)
`2) D Notice of Draftsperson's Patent Drawing Review (PTO-948)
`3) |:| Information Disclosure Statement(s) (PTO/SB/08)
`Paper No(s)/Mail Date
`.
`U.S. Patent and Trademark Office
`
`4) D Interview Summary (PTO-413)
`Paper N0(S)/IVI3” Data L
`5) I:I Notice Of Informal Patent Application
`6) D Other:
`.
`
`PTOL-326 (Rev. 08-06)
`
`Office Action Summary
`
`Part of Pa er No./Mail Date 20090415
`MYLAN x. 1024, Page2
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`MYLAN Ex. 1024, Page2
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`

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`Application/Control Number: 10/500,354
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`Page 2
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`Art Unit: 1611
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`DETAILED ACTION
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`Applicant’s response, filed 01/05/09, have been fully considered and made of
`
`record. The following rejections and/or objections are either reiterated or newly applied.
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`They constitute the complete set of actions being applied to the instant application.
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`Status of the Claims
`
`Claims 1-10 are currently pending in this application and are the subject of the
`
`Office action.
`
`Declaration
`
`The declaration of Masayo Higashiyama, received 01/05/09, has been
`
`considered and made of record.
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`The evidence submitted in support of unexpected results is not found to be
`
`sufficient to overcome the instant rejection because the exemplified preparations
`
`comprising 1.5% of bepotastine besiltate and sodium chloride 0.6% showing improved
`
`light—stability of bepotastine besilate (when compare to preparation comprising
`
`bepotastine besilate and 3.3% glucose or 3.3% manntiol) is not commensurate in
`
`scope with the instant claims. For example, instant claim 1 does not require a specific
`
`amount of bepotastine besilate or a specific “light—stabilizing effective amount" of a
`
`water—soluble metal chloride even though the study results submitted by declarant are
`
`limited to a specific concentration of bepotastine besilate of 1.5% and a concentration of
`
`sodium chloride of 0.6%. In view of the difference in scope between the exemplified
`
`MYLAN EX. 1024, Page3
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`MYLAN Ex. 1024, Page3
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`

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`Application/Control Number: 10/500,354
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`Page 3
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`Art Unit: 1611
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`data submitted by declarant and the instant claims, one would not be able to reasonably
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`or predicitably extrapolate the exemplified data to practice the instant claimed invention
`
`commensurate in scope with the claims.
`
`REJECTIONS
`
`Claim Rejections — 35 USC 112 — First Paragraph
`
`The following is a quotation of the first paragraph of 35 U.S.C. 112:
`
`The specification shall contain a written description of the invention, and of the manner and process of
`making and using it,
`in such full, clear, concise, and exact terms as to enable any person skilled in the
`art to which it pertains, or with which it is most nearly connected, to make and use the same and shall
`set forth the best mode contemplated by the inventor of carrying out his invention.
`
`Claims 1-10 are rejected under 35 U.S.C. 112, first paragraph, because the
`
`specification, while enabling for an aqueous liquid preparation comprising, in an
`
`aqueous solution, (S)—4—[4—[(4—chlorophenyl)—(2—pyridyl)—methoxy]—piperidino]—butanoic
`
`acid or a pharacmeutically acceptable acid addition salt thereof, and a low molecular
`
`weight water—soluble metal chloride in a light—stabilizing effective amount of 0.2% or
`
`more, does not reasonably provide enablement for preparations comprising any water-
`
`soluble metal chloride in a light—stabilizing effective amount of less than 0.2% , or any
`
`high molecular weight water—soluble metal chlorides. This is a scope of enablement
`
`rejection.
`
`To be enabling, the specification of the patent application must teach those
`
`skilled in the art how to make and use the full scope of the claimed invention without
`
`undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining
`
`what is meant by “undue experimentation,” the Federal Circuit has stated that:
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`MYLAN EX. 1024, Page4
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`MYLAN Ex. 1024, Page4
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`Application/Control Number: 10/500,354
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`Page 4
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`Art Unit: 1611
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`The test is not merely quantitative, since a considerable amount of experimentation is
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`permissible, if its is merely routine, or if the specification in question provides a reasonable amount of
`
`guidance with respect to the direction in which experimentation should proceed to enable the
`
`determination of how to practice a desired embodiment of the claimed invention. PPG v Guardian, 75
`
`F.3d 1558, 1564 (Fed. Cir. 1996).
`
`The factors that may be considered in determining whether a disclosure would
`
`require undue experimentation are set forth in In re Wands, 8 USPQ2d 1400 (CAFC
`
`1988) at 1404 wherein, citing Ex parte Forman 230 USPQ 546 (BdApls 1986) at 547 the
`
`court cited eight factors:
`
`1) the quantity of experimentation necessary,
`
`2) the amount of direction or guidance provided,
`
`3) the presence or absence of working examples,
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`4) the nature of the invention,
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`5) the state of the prior art,
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`6) the relative skill of those in the art,
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`7) the predictability of the art, and
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`8) the breadth of the claims
`
`These factors are always applied against the background understanding that
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`scope of enablement varies inversely with the degree of unpredictability involved.
`
`In re
`
`Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping
`
`that in mind, the Wands factors are relevant to the instant fact situation for the following
`
`reasons:
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`MYLAN Ex. 1024, Page5
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`MYLAN Ex. 1024, Page5
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`

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`Application/Control Number: 10/500,354
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`Page 5
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`Art Unit: 1611
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`The nature of the invention
`
`The invention in general relates to an aqueous liquid preparation comprising, in
`
`an aqueous solution. (S)—4—[4-[(4—chlorophenyl)—(2—pyridyl)—methoxy]—piperidino]—butanoic
`
`acid or a pharmaeutically acceptable acid addition salt thereof, and a water—soluble
`
`metal chloride in a light—stabilizing effective amount.
`
`Relative skill of those in the art
`
`The relative skill of those in the art is high, generally that of an M.D. or Ph.D.
`
`It
`
`is noted that the chemical and medical arts are generally unpredictable, requiring each
`
`embodiment to be individually assessed for chemical, pharmacologic, pharmaceutical,
`
`and clinical efficacy. The more unpredictable an area, the more specific enablement is
`
`necessary in order to satisfy the statue. (see In re Fisher, 427 F.2d 833, 166 USPQ 18
`
`(CCPA 1970)). Since the term "a light—stabilizing effective amount " is not defined by
`
`applicant, one would not be able to reasonable determine the amount of the water-
`
`soluble metal chloride that is a “light—stabilizing effective amount” without conducting
`
`extensive experimentation.
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`State and predcitability of the art
`
`Jimoh (US Patent 6,369,001) teach aqueous liquid concentrate herbicidal
`
`microemulsion compositions comprising zero to a stabilizing amount of one or more
`
`water—soluble chlorides selected from hydrochloric acid, alkali metal chlorides,
`
`ammonium chloride, low molecular weight organic ammonium chlorides and quaternary
`
`ammonium chloride surfactants (abstract), wherein said stabilizing amount is directed to
`
`provide acceptable physical stability of the microemulsion (abstract; col. 6, line 5 to col..
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`MYLAN EX. 1024, Page6
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`MYLAN Ex. 1024, Page6
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`Application/Control Number: 10/500,354
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`Page 6
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`Art Unit: 1611
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`6, line 33). Jimoh state that physical stability of the microemulsion is acceptable if no
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`significant phase separation is evident following for at least 7 days at any temperature in
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`the range from about 0° C to about 40° C (col. 6, lines 17-25). Jimoh state that is is
`
`preferred that the amount of a water-soluble quaternary ammonium choride does
`
`not exceed about 6% by weight of the composition (col. 11, lines 36-38). Jimoh
`
`teach that typical amounts of low molecular weight organic ammonium chlorides,
`
`ammonium chloride, and alkali metal chlorides and/or hydrochloric acid are those
`
`providing abut 0.5% to about 2.5% chloride ion by weight of the composition (col.
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`11, lines 60-64). Jimoh exemplifies compositions comprising ammonium chloride (cols.
`
`17-18, Examples 4-9; col. 22, Example 22) and benzalkonium chloride (cols. 20-22,
`
`Examples 13-17 and 19). Unlike the prior art wherein the water-soluble metal chlorides
`
`are employed to enhance the physical stability of an aqueous formulation (col. 11, lines
`
`14-64), the instant claims require water-soluble metal chlorides for their light-stabilizing
`
`properties. Since the physical stabilizing amount of the identical instantly claimed water
`
`soluble metal chlorides taught by the prior art overlaps with the instant claimed light-
`
`stabilizng effective amount of said water-soluble metal chlorides, there is serious doubt
`
`that one would be able to reasonably or predictably distinguish between the physical
`
`stabilizing effects and the light-stabilizing effects of the instant claimed water-soluble
`
`metal chlorides without resorting to extensive studies.
`
`The breadth of the claims
`
`The instant claims are relatively broad in scope. For example, claim 1
`
`encompasses any and all “water-soluble metal chlorides," including high molecular
`
`MYLAN EX. 1024, Page?
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`MYLAN Ex. 1024, Page7
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`Application/Control Number: 10/500,354
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`Page 7
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`Art Unit: 1611
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`water—soluble quaternary ammonium chorides and low molecular weight chlorides as
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`taugth by Jimoh (col. 11, lines 36-38). Further, applicant’s test results show that only
`
`preparations comprising a water—soluble metal chloride in not less than 0.2 w/v%
`
`improved the stability of bepotastine besilate under light irradiation conditions (page 8,
`
`lines 6-15, including Table 1). However, claim 2 recites “wherein the iiieiai cE'iEoi‘Edi=3 has
`
`:3: conci=3nts':a=*.ioi"i selected
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`the range of 3 Eowsr iimii cosiceiitration of i3.i5% w.-’\.e‘%
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`and an up-pea" limit concentration of 1.5 wfvél-ii," whicii is less than
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`also
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`specification, page 3, lines 2-21). Besides, as discussed above, the term “a light-
`
`stabilizing effective amount” as recited in claim 1, does not require a specific “light
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`stabilizing amount” of a "water—soluble metal chloride" even though applicant discloses
`
`that concentrations less than 0.2% does not improve the stability of the instant claims
`
`aqueous liquid preparations. Hence, one would not be able to reasonably practice the
`
`instant claimed invention commensurate with the scope ofthe claims since the instant
`
`claims encompass preparations comprising water—soluble metal chloride in an amount
`
`of less than 0.2% even though applicant's test results show that concentrations less
`
`than 0.2% is devoid of light—stabilizing effect (page 8, lines 6-15, including Table 1).
`
`The amount of direction or guidance provided and the presence or absence of
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`working examples
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`The specification discloses specific formulations comprising benzalkonium
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`chloride alone in an amount of 0.005% (specification, page 12); benzalkonium chloride
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`0.005% and sodium chloride in concentrations ranging from 0.79% — 0.6%
`
`(specification, pages 13-16). However, applicant states that no improvement in stability
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`MYLAN EX. 1024, Page8
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`MYLAN Ex. 1024, Page8
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`Application/Control Number: 10/500,354
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`Page 8
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`Art Unit: 1611
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`was observed with formulations comprising less than 0.2% of a water—soluble metal
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`chloride (page 9, lines 10-20). Since the examples are limited to low molecular metal
`
`chlorides, one would expect to reasonably extrapolate the instant exemplified data to
`
`the genus of water—soluble metal chlorides in view of the teaching of Jimoh showing
`
`that the stabilizing amount of the high molecular weight metal chloride and low
`
`molecular weight metal chlorides vary substantially from each other (e.g. a water
`
`soluble quaternary ammonium choride in amounts up to about 6% by weight, col. 11,
`
`lines 36-38; and low molecular weight organic ammonium chlorides, ammonium
`
`chloride, and alkali metal chlorides and/or hydrochloric acid are those providing about
`
`0.5% to about 2.5% chloride ion by weight of the composition; col. 11, lines 60-64).
`
`The guantity of experimentation necessary
`
`In view of the uncertainty and unpredictability of the art as evidenced by the
`
`discussion of the prior art, it is reasonable to surmise that this level of uncertainty in the
`
`art would require one skilled in the art to conduct more than routine experimentation in
`
`order to practice the claimed invention commensurate with the scope of the claims.
`
`For the reasons stated above, claims 1-10 are rejected under 35 USC 112, first
`
`paragraph, for lack of scope enablement because the specification does not enable any
`
`person skilled in the art to which it pertains, or with which it is most nearly connected, to
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`practice the invention commensurate in scope with the claims.
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`MYLAN EX. 1024, Page9
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`MYLAN Ex. 1024, Page9
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`Application/Control Number: 10/500,354
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`Page 9
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`Art Unit: 1611
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`Claim rejections — 35 USC 103(a)
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`The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all
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`obviousness rejections set forth in this Office action:
`
`(a) A patent may not be obtained though the invention is not identically disclosed
`
`or described as set forth in section 102 of this title, if the differences between the
`
`subject matter sought to be patented and the prior art are such that the subject
`
`matter as a whole would have been obvious at the time the invention was made
`
`to a person having ordinary skill in the art to which said subject matter pertains.
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`Patentability shall not be negatived by the manner in which the invention was
`
`made.
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`This application currently names joint inventors.
`
`In considering patentability of
`
`the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of
`
`the various claims was commonly owned at the time any inventions covered therein
`
`were made absent any evidence to the contrary. Applicant is advised of the obligation
`
`under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was
`
`not commonly owned at the time a later invention was made in order for the examiner to
`
`consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g)
`
`prior art under 35 U.S.C. 103(a).
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`MYLAN EX. 1024, Page10
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`MYLAN Ex. 1024, Page10
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`Application/Control Number: 10/500,354
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`Page 10
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`Art Unit: 1611
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`Claims 1-10 are rejected under 103(a) as being unpatentable over Kita et al
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`(US Patent 6,307,052 B1; already made of record), Stevenson et al. (US Patent
`
`4,053,628).
`
`Kita et al. teach a benzenesulfonic acid salt and a benzoic acid salt of (S)—4—[4-
`
`[(4-chlorophenyl)-(2-pyridyl)-methoxy]-piperidino]-butanoic acid as having excellent
`
`antihistaminic activity, anti—allergic activity, and excellent in physiochemical stability so
`
`that they are particularly suitable as a medicine (abstract; and col. 1, lines 11-21). Kita
`
`et al. teach antihistaminic compounds for use in the treatment of, for example, allergic
`
`skin disease, dermatitis, allergic rhinitis, sneeze ,
`
`and bronchial asthma (col. 1, lines
`
`24-53). Kita et al. teach that the acid addition salt has little hydroscopicity and excellent
`
`physiochemical stability so that it is a particularly suitable compound as a medicine for
`
`allergic skin diseases, allergic rhinitis, sneeze, mucus, cough due to respiratory
`
`inflammation such as a cold, and bronchial asthma (column 1, lines11-54).
`
`Kita et al. does not teach aqueous liquid preparation comprising a water—soluble
`
`metal chloride.
`
`Stevenson et al. (US Patent 4,053,628) teach aqueous solution (e.g. eye and
`
`nasal solutions) preparations, including eye compositions comprising one or more
`
`compounds which are therapeutically useful in the eye, wherein said one or more
`
`therapeutically useful compounds include an anti—allergic agent (e.g. anti—histamines
`
`such as antazoline or diphenhydramine hydrochloride;abstract; col. 3, lines 10-16; col.
`
`5, Examples 1-2). Stevenson et al. teach that the additional compounds may be present
`
`MYLAN EX. 1024, Page11
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`MYLAN Ex. 1024, Page11
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`Application/Control Number: 10/500,354
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`Page 11
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`Art Unit: 1611
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`at a concentration of from about 0.05 to 0.6% w/v (col. 3, lines 31-34). Stevenson et al.
`
`state that the concentration of the additives in the solution may be in the range 0.25 to
`
`5% w/v (col. 4, lines 1-7). Stenvenson et al. teach that the preferred pH for maximum
`
`stability is from 4 to 7.5 (col. 3, lines 2-6). Stevenson et al. teach methods of treatment
`
`of conditions of the eye comprising the use of additional therapeutically useful
`
`compounds separately from, but simultaneously with the compositions (col. 3,
`
`lines 38-45). Stevenson et al. exemplify eye drop solution comprising sodium chloride,
`
`for example 0.56% w/v {t::eis. 5--6, tE>:emt:-ie 'i etiti 3). §3tevehsei'z
`
`et. £-3><@tt’i§)tt‘fj;i e
`
`preserved buttered isetehis eye-strep S{}ELEtit3*E": sehierisihg seeztiiim ehieriee 0.42% ‘~.sW'\»’
`
`(set. 6, Exshnpe 3). Stevehsen ei st. teeeh eemeesitéehs fer use in the treatment et eye
`
`C{)t’idt’tiGi”‘tS, ihettteiiwg the eettiei" eiteets et iwey fever, etierigc eyes stieh es
`
`seritigisiirhttier t:erijt.:ht:tiv'itEs ieei. 4,
`
`{SS te mi. 52,
`
`2?’). §%3tem*ehseh et et. ieeeti
`
`eem_;3esi'tEehs “tea” treetirig hes;-si ~i}~i:3E":{ititisi.‘st'tS, iiteiudiitg hssei rhinitis {set 5, times 8-13}. it
`
`weuie have heeh ehvietis te s perseh et sitéii ih
`
`art at the time the itwehtéeh Wes
`
`mesie te eeihhihe the teeshirigs at the eitee‘ i'ei°erehces by etitiihg (S)—4—[4—[(4-
`
`chlorophenyl)-(2-pyridyl)-methoxy]-piperidino]-butanoic acid) as taught by Kida et al. to
`
`an aqueous liquid composition comprising sodium chloride as taught by Stevenson et
`
`al. to treat an allergic condition (e.g. conjunctivitis or hay fever). One would have been
`
`motivated to do so because Stevenson et al. suggest aqueous solution compositions
`
`comprising one or more compounds which are therapeutically useful for topical
`
`application (e.g. eye, nose), wherein said one or more therapeutically useful compounds
`
`include an anti—allergic agent (e.g. anti—histamines; col. 3, lines 10-16) for separate
`
`MYLAN EX. 1024, Page12
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`MYLAN Ex. 1024, Page12
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`Application/Control Number: 10/500,354
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`Page 12
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`Art Unit: 1611
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`administration (col. 3, lines 38-45) to treat allergic conditions (e.g. conjunctivitis; col. 4,
`
`lines 59-66 ) and Rita et ai. isE%<’EiCi’i tne identicei inetentiy ciainned cniiipnund, (S)—4—[4—[(4—
`
`chlorophenyl)—(2—pyridyl)—methoxy]—piperidino]—butanoic acid), es being §'.”.iEl~i”ii€3tiiEii"iy
`
`siiiiainie
`
`za nietiitzine ins“ treating é.‘iii~‘I~}i’s§_§i{) rhinitis aiitri si'ieezing (column 1, lines11—54),
`
`which is also an antihistamine drug.
`
`Regarding ciaiin ‘i, Kids et
`
`teecn (S)—4—[4—[(4—chlorophenyl)—(2—pyridyl)—
`
`methoxy]—piperidino]—butanoic acid).
`
`With respect to the term “a water—soluble metal chloride in a light—stabilizing
`
`effective amount,” Stevenson et al. exemplify aqueous eye drop solution comprising
`
`sodium chloride 0.56% w/v, and 0.42% icnisi 5&3, Exeinnie i
`
`3}, wnicn i'e:9.e's en
`
`the instant cieirneti iiinitatien since S{‘3Ci'iiii”i”i chinnde is e watensniiibie nietai ehieride.
`
`Since t:oi'it:ei'itrntions oi’ i~}t)€.‘iiiji’Ti chioiitie ni 0,5€S% and
`
`as i;é_‘iLigiiE by tiie
`
`Stevensnn et
`
`nvei'ieps witi'i the £ai“i'iGt,ii’ii cit snni=.in'i eiiinrine discieseti by zapniieant
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`being :3: ”iight~stni3iEi;:in§ effective amount (specification, page 8, lines 6-15, including
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`Table 1), one would reasonably except that the sodium chloride component of the
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`aqueous liquid preparations encompassed by the prior art, wherein said sodium chloride
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`is present in an amount of 02% or more (e.g. 0.56%) would also be a light—stabilizing
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`effective amount absent objective evidence to the contrary.
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`Regarding the preamble, Stevension et al. teach aqueous liquid solutions
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`(abstract; and col. 5, Example 1).
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`Re§iai'i:iiiig ciairn 2, Stevenson et al. exemplify aqueous eye drop solution
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`comprising sodium chloride 0.56% w/v iceis, £343‘), Exeinpie
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`a.ni:i 3}, wnicn reeds nn tne
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`MYLAN EX. 1024, Page13
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`MYLAN Ex. 1024, Page13
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`

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`Application/Control Number: 10/500,354
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`Page 13
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`Art Unit: 1611
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`term
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`the range of
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`lower‘
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`concentration of
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`w;‘v‘"ir£; and an Li§;3§3€:3E”
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`iimi't
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`txsrtzentration of ‘E .5 wiv‘§i’e.
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`Regarding claim the above discussion of
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`is incorporated by reference.
`
`Regarding claim 4», Stevertsort et al. s=_=3>:et‘nt:-iify compositions wherein the
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`tites'ape3L:ticaiiy effective agent is
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`§3~i:‘E":§':tE¥E":ii‘§§5:§{}ii of ranging from ’i»:iE% and sodium
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`chloride in a range of {M2 to 0.50% (sols. 5%}, Examples ‘LEE; such that one would
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`reasonably
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`to rely on the teaching; of S§teyenst§n at
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`in
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`an aqueous
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`iiqtiitzi preparation comprising an é3i’i‘tih§C~3‘§€«:i‘n§i‘i:’:‘.é
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`(egg. (S)—4—[4—[(4—chlorophenyl)—(2—
`
`pyridyl)—methoxy]—piperidino]—butanoic acid) in a concentration of 1—2%, which overlaps
`
`with the instant claimed amount of (S)—4—[4—[(4—chlorophenyl)—(2—pyridyl)—methoxy]—
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`piperidino]—butanoic acid of “0.1 to 2%, for separate administration absent objective
`
`evidence to the contrary.
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`Reggarding claims 543, Kits at
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`teach benzenesulfonic acid salt and a benzoic
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`acid salt of (S)—4—[4—[(4—chlorophenyl)—(2—pyridyl)—methoxy]—piperidino]—butanoic acid,
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`which are acid addition salts (abstract; and col. 1, lines 11-21), which reads on the
`
`instant claims.
`
`Regarding claim 7, Stevenson et al. teach that the preferred pH for maximum
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`stability is from 4 to 7.5 (col. 3, lines 2-6) and the instant claims recite "a pH in the range
`
`of 4-8.5" and therefore one would reasonable expect to successfully prepare aqueous
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`liquid formulations having a pH of 4-7.5 as encompassed by the prior art since the pH of
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`the prior art and the instant claims overlap absent objective evidence to the contrary.
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`Regarding claim 8, Stevenson et al. teach eye drop (abstract; col. 5, Example 1).
`
`MYLAN EX. 1024, Page14
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`MYLAN Ex. 1024, Page14
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`

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`Application/Control Number: 10/500,354
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`Page 14
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`Art Unit: 1611
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`Regarding caim 9, Stevenson et al. teach nasal spray solution (col. 5, Example
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`2), which reads on the term "nasal drop" because the nasal spray solution when
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`sprayed is delivered (or dropped) into the nose.
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`Regartiirig ciaim 1&3, iiita ei al. teach benzenesulfonic acid salt and a benzoic
`
`acid salt of (S)—4—[4—[(4—chlorophenyl)—(2—pyridyl)—methoxy]—piperidino]—butanoic acid,
`
`which are acid addition salts (abstract; and col. 1, lines 11-21) and Stevenson et al.
`
`suggest that aqueous eye solutions comprising a therapeuticially effective agent for
`
`treating an eye condition (e.g. an antihistamine) and sodium chloride in a concentration,
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`for example, 0.5% and an antihistamine are physically stable. Since the prior art
`
`encompasses aqueous eye solutions comprising sodium chloride in an amount reads
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`on the instant claimed amount of sodium chloride of "not less than 0.2 w/v% and not
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`more than 0.8 w/v%” one would also expect that said amount of sodium chloride as
`
`taught by the prior art would also be an amount that is "a light—stabilizing effectice
`
`amount.
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`Response to applicant's arguments
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`Applicant's arguments with respect to the rejection under 103(a) have been
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`considered but are moot in view of the new ground(s) of rejection. However, the merits
`
`of Kita et al. is maintained.
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`In response to applicant's argument that Kita does not teach the combination of
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`said compound with any water—soluble metal chloride, it is the examiner’s position that
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`Stevenson et al. suggest the use of aqueous topical solutions comprising sodium
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`chloride and an antihistamine agent for treating aiiergic cosiditiosis
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`coiiiunciévétis,
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`MYLAN EX. 1024, Page15
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`MYLAN Ex. 1024, Page15
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`

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`Application/Control Number: 10/500,354
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`Page 15
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`Art Unit: 1611
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`hey ‘fetter;
`
`tine 51% te eet. 5, Eétte t3} ettet
`
`et et.
`
`the tdetttteet Etttstentty
`
`eéeémect esttttéetemtne (:(3t't’tt:3(3Ltt“:t.‘§ te pertteuteriy
`
`ee e meeéeétte fer
`
`ettetgte t“§"t§t”tEt§S and etteezittg. S§§t”‘tC{-3 the t:-tier
`
`etteemt:-eeeee er: eetteette itqtttft
`
`t:%t£%t:%€%t’&3t§{}tt
`
`{3(3t't't§;.’tt“§&3§t‘:g the tt.t'ettttt:et §i‘t;~3té§t":E§§,i t:EeEmes:t' entitttetemttte t:etttt3et.sttt:5 etttt
`
`eedttmt t:ttiettt:te in e eeneentretéett
`
`"fer exetttpée, 0.5t3~5% end the Ettetent eteittte etee
`
`require en t~Ett’?;ttt’:%t3US Eéttttitt pteperetten C-Qt‘Tt§£)E”tS§t't§ the ieetttteet tttetetttiy eéeémee
`
`etttittéetemétte eetttt:-etmtt es tettgttt ttay the §L)§'"tC3E" art and 3 wetet~eetut3Ee
`
`t_”:§“t§t.‘§i"§C'{-3
`
`{egg}, eetttttm t:tttertt:5e} in e Eig_tttt—-etetxéttztttg et‘t‘et::ttve emettttt that {}\e‘t.‘-3i“§éE§)&3 with the _t3s“it”.ss”
`
`3?‘; ene wettte t'eeeene‘ety exeeett that the ettgtseeue tteuée preperetten etteetttpeeeee téy
`
`the §‘Ztt’ttitt' est weute eiee be eeeebte et tterferstttngt the tntetttted futtetéert euett that the
`
`Ett”t”t{§t£t"=‘-i
`
`WEEK-Btfififtittbte tttetet etttetétte
`
`eeetttm etttetttte} te
`
`ttgttt~etet3tEEzEttg
`
`ettetzttve &3tt’tt)ttF‘:t.
`
`Wtttt teepetzt te epeééeewe eeeertéett
`
`unexpected teeuéte,
`
`eteeve déeeeeetert
`
`Eat eeatneetéezt with the reeeettee te the tteeterettett Ee tneereeretee
`
`reference.
`
`‘tttuss, wettttt ttette feeert etwétttte tie e peteert et’ Siitti in the est et the téme the
`
`Et'tvet'tttet't wee matte te t3t”E3éi‘-It-3
`
`Ettetettt
`
`§i‘W£-3t'ttt(}t't with t*ees;t::net>ie E33<j§.3t-3t22t3.‘i§{}tt
`
`etteeeee.
`
`Relevant Art of Record
`
`The below art reference made of record and relied upon is considered pertinent to
`
`app|icant’s invention.
`
`MYLAN EX. 1024, Page’|6
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`MYLAN Ex. 1024, Page16
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`Application/Control Number: 10/500,354
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`Page 16
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`Art Unit: 1611
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`Onuki et al. (US Patent Application Pub. No. 2004/0147605;a|ready made of
`
`record) teach formulations comprising one or more antihistamine compound, including
`
`bepotastine besilate (page 2, para 0017, line 11).
`
`Himmelstein et al. (US Patent 5,599,534; already made of record) teach pH-
`
`responsive reversible gelling compositions and liquid formulations for sustained delivery
`
`of therapeutic or diagnostic agents suitable for use as drop or spray instillable or topical
`
`drug delivery vehicles for drugs various drugs, including antihistamines and
`
`decongestants (e.g. pyrilmaine, chlorpheniramine, tetrahydrazoline, antazonline),
`
`which are particularly suitable for delivering pharmaceutical compounds to the ocular
`
`environment due to clarity and lubricating properties of the gel
`
`(col. 5, lines 32-49 and
`
`col. 8, line 51 to col. 9, line 9); flowable liquid forms of the composition are particularly
`
`useful for pharmaceutical formulations to be applied by drops (e.g. eye drops) or sprays
`
`(e.g. nasal sprays). See col. 7, lines 49-59; and col. 8, lines 29-34. Himmelstein et al.
`
`teach that the pH preferably is within the physiological range between pH 2.5 and 7.5
`
`(col. 6, lines 35-39).
`
`Kabra (US Patent 6,331,540) teach a method of enhancing the stability of an
`
`aqueous pharmaceutical composition containing fluoroquinolone and xantham gum and
`
`the step of adding to the composition a water-soluble calcium salt in an amount of at
`
`least 0.15 % (w/w), such that the composition is homogenous and has a turbidity rating
`
`(NTU) < = 40 at room temperature (see cols. 5-6, including Table 3 and reference claim
`
`1).
`
`MYLAN EX. 1024, Page17
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`MYLAN Ex. 1024, Page17
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`

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`Application/Control Number: 10/500,354
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`Page 17
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`Art Unit: 1611
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`Any inquiry concerning this communication or earlier communications from the
`
`examiner should be directed to Charlesworth Rae whose telephone number is 571-272-
`
`6029. The examiner can normally be reached between 9 a.m. to 5:30 p.m. Monday to
`
`Fnday.
`
`If attempts to reach the examiner by telephone are unsuccessful, the examiner’s
`
`supervisor, Sharmila G. Landau, can be reached at 571-272-0614. The fax phone
`
`number for the organization where this application or proceeding is assigned is 571-
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`273-8300.
`
`lnformation regarding the status of an application may be obtained from the
`
`Patent Application Information Retrieval (PAIR) system. Status information for
`
`published applications may be obtained from either Private PAIR or Public PAIR.
`
`Status information for unpublished applications is available through Private PAIR
`
`only. For more information about the PAIR system, see http:pair-direct.uspto.gov.
`
`Should you have any questions on access to the Private PAIR system, contact the
`
`Electronic Business Center (EBC) at 800-217-9197 (toll-free).
`
`If you would like
`
`assistance from a USPTO Customer Service Representative or access to the
`
`automated information system, call 800-786-9199 (IN USA OR CANADA) or 571 -272-
`
`1000.
`
`16 April 2009
`
`/C. R./ Examiner, Art Unit 1611
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`MYLAN EX. 1024, Page18
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`MYLAN Ex. 1024, Page18
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`

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`Application/Control Number: 10/500,354
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`Page 18
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`Art Unit: 1611
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`/Sharmila Gollamudi Landaul
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`Supervisory Patent Examiner, Art Unit 1611
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`MYLAN EX. 1024, Page’|9
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`MYLAN Ex. 1024, Page19